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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5361_Библиотеки_им_академика_М_И_Перельмана.pdf
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- •Aim and Scope
- •Preface
- •Acknowledgments
- •Contents
- •Contributors
- •About the Editors
- •1.1 Introduction
- •1.2.1 Friction
- •1.2.1.3 Friction Under Lubricated Conditions
- •1.7.1 Joint Tribology
- •1.7.2 Skin Tribology
- •1.7.3 Oral Tribology
- •1.8 Summary
- •References
- •2.1 Introduction
- •2.3.1 Fluid Pressurization/Fluid-Film Lubrication
- •2.3.2 Boundary Lubrication
- •2.3.3 Hydrodynamic Lubrication
- •2.3.4 Squeeze-Film Lubrication
- •2.3.5 Synovial Fluid
- •2.3.6 Hydration Lubrication
- •2.5.2 Scaffolds
- •2.5.3 Synthetic Polymer
- •2.5.4 Polyacrylamide
- •2.5.5 PEG Hydrogel
- •2.5.6 PVA Hydrogel
- •2.5.7 Double Network Hydrogel
- •2.5.8 Triple Network Hydrogel
- •2.6.1 Polyacrylamide
- •2.6.2 PEG Hydrogel
- •2.6.3 PVA Hydrogel
- •2.6.4 Double Network Hydrogel
- •2.6.5 Triple Network Hydrogel
- •2.7.1 Mechanical Properties
- •2.7.2 Structural Properties
- •2.8 Conclusion
- •References
- •3.1 Introduction
- •3.3.1 Label-Based Biosensors
- •3.3.2 Label-Free Biosensors
- •3.4 Different Nanobiosensing Techniques
- •3.4.1 Optical Sensing
- •3.4.2 Electrochemical/Electrical Sensing
- •3.4.3 Magnetic Sensing
- •3.4.4 Mass-Based Sensing
- •3.6.2 Neurodegenerative Diseases
- •3.6.3 Infectious Diseases
- •3.6.4 Metabolic Diseases
- •References
- •4.1 Introduction
- •4.2.1 Surface Functionalization
- •4.2.2 Bioconjugation
- •4.3 Synthesis Approach
- •4.3.1 Hydrothermal Method
- •4.3.2 Chemical Vapor Deposition (CVD)
- •4.3.3 Wet Chemical Method
- •4.4 Plasmonic Black Bodies (PBBs)
- •4.4.1 Gold NP (AuNPs)-Based PBB
- •4.4.2 Silver NPs (Ag NPs)-Based PBB
- •4.4.3 Platinum NPs (Pt NPs)-Based PBB
- •4.5 Biomimetic NP
- •4.6 Upconverting NP (UCNP)
- •4.6.1 Synthesis
- •4.7 Inorganic NP
- •4.7.1 Synthesis
- •4.8 Photothermal Therapy (PTT)
- •4.9 Conclusion
- •References
- •5.1 Introduction
- •5.2 Human Skin
- •5.10 Future Scope
- •5.11 Conclusion
- •References
- •6.1 Introduction
- •6.1.1 Class 1
- •6.1.2 Class 2
- •6.1.3 Class 3
- •6.4.1.1 Surface Patterning
- •6.4.1.2 Direct-Write Patterning
- •6.4.1.5 Dip-Pen Nanotechnology
- •6.4.1.7 Composing Using Beams
- •6.4.1.8 Direct Write Photolithography (DWP)
- •6.4.1.9 Light-Beam Lithography Electron
- •6.4.1.10 Focused Ion Beam Lithography
- •6.4.2 Fabrication Techniques
- •6.4.2.4 Non-invasive Glucose Monitoring Devices Technique
- •6.4.2.6 Cost-Effective Electrochemical Voltametric Sensors Techniques
- •6.4.2.7 Three-Dimensional (3D) Printing Techniques
- •6.4.2.8 UV-LED Stereolithography Printer Technique
- •6.4.2.9 4D Printing Techniques
- •6.4.2.10 Advanced Biomedical Techniques Involving Biorobots
- •References
- •7.1 Introduction
- •7.6 Mechanical Biocompatibility Challenges
- •7.7 Poor Bio-Printing Resolution
- •7.9 Limited Biomaterial Selection
- •7.11 Conclusion
- •8.2 Animal Tribology
- •8.2.1 Joint
- •8.2.3 Integumentary Change
- •References
- •8.1 Introduction
- •8.3.1 Nanotribology
- •8.4 Green Tribology
- •8.5 Conclusion
- •References
- •9.1 Introduction
- •9.2 Bio-Tribological Issues
- •9.3.2 Bone Fracture Fixation
- •9.3.4 Cardiovascular Devices
- •9.3.5 Minimal Invasive Surgical Devices
- •References
- •10.1 Introduction
- •10.2.2.1 Structural Integrity
- •10.2.2.2 Controlled Release Properties
- •10.2.2.3 Enhanced Drug Loading Capacity
- •10.2.2.4 Tailored Material Properties
- •10.2.3.1 Biocompatibility
- •10.2.3.3 Mechanical Properties
- •10.2.3.4 Drug Compatibility
- •10.2.3.5 Fabrication Compatibility
- •10.3.1 Matrix Material Properties
- •10.3.4 Biocompatibility Assessment
- •10.3.4.1 In Vitro Cell Culture Studies
- •10.3.4.2 Hemocompatibility Studies
- •10.3.4.3 In Vivo Animal Studies
- •10.3.4.4 Histological Analysis
- •10.3.4.5 Immune Response Evaluation
- •10.3.4.6 Biodegradation Assessment
- •10.4 Surface Engineering Considerations
- •10.4.2.1 Surface Coatings
- •10.4.2.2 Plasma Treatment
- •10.4.2.3 Surface Grafting
- •10.4.2.4 Dip Coating
- •10.4.2.5 Spray Coating System
- •10.4.2.6 Electrotreated Coating
- •10.4.2.9 Microfabrication Techniques
- •10.4.2.10 Surface Roughness Control
- •10.5.1.2 Mechanical Properties
- •10.5.1.3 Surface Characteristics
- •10.5.1.4 Release Kinetics Analysis
- •10.5.1.5 Biological Compatibility
- •10.5.1.7 Other Analyses
- •10.6 Advanced Fabrication Techniques
- •10.8 Conclusion
- •References
- •11.1 Introduction
- •11.2 Shape Memory Alloys (SMA)
- •11.3 Shape Memory Polymers
- •11.3.1 Heat
- •11.3.2 Light
- •11.3.3 Magnetic Field
- •11.4 Shape-Changing Hydrogels
- •11.5 Biomedical Applications
- •11.6 Conclusion
- •References
- •12.1 Introduction
- •12.3 Bioresorbable Orthopedic Implants
- •12.4.1 Polylactides
- •12.4.2 Poly (Ortho Esters)
- •12.4.3 Polyphosphoesters
- •12.4.4 Polyphosphazenes
- •12.4.5 Polycaprolactone
- •12.4.6 Polyurethanes
- •12.4.7 Polycarbonates
- •12.5.1 Compression Molding
- •12.5.2 Transfer Molding
- •12.5.3 Injection Molding
- •12.5.4 Extrusion
- •12.5.5 Blow Molding
- •12.5.6 Calendering Process
- •12.5.7 Fiber Spinning
- •12.5.8 Thermoforming
- •12.5.9 Polymer Foaming
- •12.7 Challenges
- •12.8 Conclusion
- •References
- •13.1 Introduction
- •13.3.1.1 Total Hip Replacement (THR)
- •13.3.2 Resurfacing Hip Replacement (RHR)
- •13.5.1 Adhesive Wear
- •13.5.2 Abrasive Wear
- •13.5.3 Fatigue Wear
- •13.5.4 Corrosion/Oxidative Wear
- •13.5.5 Surface Cracking
- •13.6.1 Metallic Implants
- •13.6.1.1 Stainless Steel
- •13.6.1.2 Co-Cr Alloys
- •13.6.1.3 Ti-Alloy
- •13.6.2 Ceramic Implants
- •13.6.3 Polymer Implants
- •13.6.4 Composite Implants
- •13.6.5.2 Surface Coatings
- •13.7.2.1 Hydrodynamic Lubrication
- •13.7.2.2 Boundary Lubrication
- •13.7.2.3 Elastohydrodynamic Lubrication
- •13.7.3 Biomimetic Lubrication Approaches
- •13.7.3.1 Replicating Natural Lubrication Mechanisms
- •13.7.4.1 Implant Wear
- •13.7.4.3 Synovial Fluid Degradation
- •13.8.1 Hydroxyapatite Coatings
- •13.8.1.1 Bone Integration
- •13.8.1.2 Implant Stability
- •13.8.1.4 Biocompatibility
- •13.8.2 Diamond-Like Carbon Coatings
- •13.8.3 Metal Nitride Coatings
- •13.8.4 Polymeric Coatings
- •13.8.5 Nanocomposite Coatings
- •13.9.1 Pin-on-Disk Testing
- •13.9.2 Hip Joint Simulators
- •13.9.3 Knee Joint Simulators
- •13.9.4 Tribo-Corrosion Testing
- •13.9.5 Wear Debris Analysis Techniques
- •13.9.5.1 Scanning Electron Microscopy (SEM)
- •13.9.5.2 Energy-Dispersive X-Ray Spectroscopy (EDS)
- •13.10.1.1 Tailored Geometries
- •13.10.1.2 Improved Wear Characteristics
- •13.10.1.3 Accelerated Innovation
- •13.10.2.1 Real-Time Wear Monitoring
- •13.10.2.2 Functionality Assessment
- •13.10.2.3 Implant Status Monitoring
- •13.10.2.4 Patient-Centric Healthcare
- •13.10.3.1 Advanced Biomaterials
- •13.10.3.4 Multidisciplinary Approaches
- •13.10.4.1 Wear Data Analysis
- •13.10.4.2 Predictive Wear Patterns
- •13.10.4.3 Early Intervention Strategies
- •13.10.4.4 Personalized Treatment Plans
- •13.11 Conclusion
- •References
- •14.1 Introduction
- •14.2.1 Powder Bed Fusion (PBF)
- •14.2.2 Directed Energy Deposition
- •14.3.1 Extrusion-Based AM
- •14.5 Biomanufacturing
- •14.5.1 Tissue Engineering
- •14.5.2 Organ-on-a-Chip Models
- •14.6 Conclusion
- •References
- •Index

4 Biological Smart Materials: Materials forCancer Treatment
123
and binding afnity to target cells, further improving drug delivery efcacy [59]. In
theranostics, Pt PBBs can play a role in both therapeutic and diagnostic functions.
Their plasmonic properties offer opportunities for enhanced imaging capabilities,
acting as contrast agents in techniques such as photoacoustic imaging and dark-eld
microscopy. Pt NPs have enhanced picture contrast and resolution, making it possible to precisely see biological structures and processes. This enables real-time
medication delivery monitoring, treatment response evaluation, and visualization of
therapeutic effectiveness [60]. However, it is important to note that Pt NPs are more
expensive and less readily available compared to Au and Ag NPs. Additionally, their
plasmonic behavior occurs in a range that has limitations for tissue penetration,
which may impact their applications in certain contexts. Further investigations are
being conducted to optimize Pt NP synthesis, improve their stability, and explore
their specic advantages in photocatalysis, sensing, and optoelectronics for targeted
applications in the biomedical eld. In the study conducted by Qi etal. [61], Pt@
PDA-c NPs were synthesized using a specic method. Initially, dopamine hydrochloride was mixed with NaHCO3-HCl buffer, and then a K2PtCl4 solution was
added. The reaction proceeded, resulting in the formation of a solid product, which
was subsequently collected, washed, and dispersed in deionized water. To cap the
NPs with polyethylene glycol (PEG), a PEG-SH solution was introduced.
Additionally, an anti-CXCR4 antibody was loaded onto the NPs. The resulting NP
dispersion underwent centrifugation, washing, and lyophilization steps to obtain the
nal Pt@PDA-c NPs as shown in Fig.4.2a. The size of the NPs, determined through
TEM and DLS measurements, was found to be approximately 150nm as shown in
Fig. 4.2b, c and the UV-Vis spectroscopy (Fig. 4.2d) shows the broad range of
absorption, i.e., 500nm to 1100nm which will be benecial for the PTT application
(Fig.4.2e). Pt@PDA-c aqueous dispersions’ suggested UV-VIS spectra at various
concentrations. Figure 4.2f represents the temperature elevation curves of Pt@
PDA-c during laser irradiation (1064nm, 1W•cm2) at various concentrations, and
Fig. 4.2g shows the photothermal heating and cooling cycles of Pt@PDA-c
(0.25mgmL1) under 1W•cm2 of 1064nm laser illumination. The efciency of the
photothermal conversion was 71.3%.
4.5 Biomimetic NP
The convergence of nature’s ingenious designs and cutting-edge cancer therapy has
given rise to the burgeoning eld of biomimetic-based NPs. This innovative
approach draws inspiration from the intricate processes and materials that have
evolved over millions of years, harnessing their blueprint to revolutionize cancer
treatment. Biomimetics, or biomimicry, involves mimicking natural processes,
structures, and materials to solve complex problems like cancer treatment [62]. By
replicating biological mechanisms, researchers create NPs, liposomes, and nanodevices that can target cancer cells precisely, deliver therapeutic agents, and respond
to specic stimuli in the TME for controlled drug release [63]. These are typically

124
Fig. 4.2 Synthesis and characterization of Pt nanomaterial. (a) Synthesis process of NP. (b) TEM
image. (c) DLS image of synthesis NP. (d) Broad range of absorption. (e) Pt@PDA-c aqueous
dispersions’ UV-VIS spectra at various concentrations. (f) Pt@PDA-c temperature rise curves
under laser irradiation at various concentrations. (g) Photothermal heating & cooling cycles of Pt@
PDA-c. (h, i) The accumulation of NPs in the tumor reached its peak at around 12h after injection.
(j, k) Laser irradiation of the tumor site using Pt@PDA-c NPs and tumor region’s local temperature raised quickly to 55°C in 5 min under 1064nm laser irradiation. (l) Treatment period, the
body weight measurement. (m) Tumor development curves and tumor relative volume, while control groups. (Reprinted with permission from Elsevier [61])
D. Panda etal.
coated with cell membranes or functionalized with biomolecules, enabling them to
interact with biological systems in a manner similar to natural cells or tissues. The
signicance of biomimetic NPs lies in their ability to overcome some of the major
challenges in traditional drug delivery systems, such as poor targeting, low drug
stability, and systemic toxicity [64]. By leveraging biomimicry, these NPs can
improve drug delivery efciency, enhance therapeutic efcacy, and minimize offtarget effects, making them highly promising for advanced nanomedicine applications. These advancements hold the potential to revolutionize cancer therapies by
enabling precision targeting tailored to individual patients. These biomimetic materials are meticulously designed to identify and attach to cancer cells using molecular interactions, ensuring that therapeutic agents accumulate precisely at the tumor
site. This approach minimizes harm to healthy tissues, thus enhancing the effectiveness of treatment while mitigating side effects [65]. Biomimetic materials for cancer treatment offer the remarkable ability to adapt to the unique conditions of the
TME.These materials can sense changes in pH levels or enzyme activity, triggering
controlled release of therapeutic agents exclusively at the tumor site, reducing offtarget effects. By mimicking the structural and biochemical aspects of the TME,
biomimetic platforms provide more accurate models for studying cancer behavior
and evaluating potential treatments [66]. Personalized treatments tailored to individual patient characteristics, combined with other therapies, lead to synergistic

4 Biological Smart Materials: Materials forCancer Treatment
125
effects and increased treatment success. Biomimetic NPs (NPs) can be created
using various techniques, each allowing precise control over size, drug loading, and
surface properties. Techniques such as nanoprecipitation and extrusion enable the
development of drug-loaded NPs, while self-assembly leverages biomolecules’
natural tendencies to form NPs with specic functions. By utilizing diverse biomolecule sources and fabrication methods, researchers can design effective and targeted
drug delivery systems, advancing precise and efcient cancer treatments [67].
Although this is still in research, it’s full of promise and could change how we treat
cancer, using smart ideas inspired by nature. The versatility of these biomimetic
materials opens up new avenues for scientic advancement, addressing complex
challenges across various disciplines. The study conducted by Chirivì etal. [68]
focused on synthesizing biomimetic NPs for potential PTT applications in a 3D
glioblastoma tumor model. First, the researchers used the Turkevich technique
using sodium citrate as a reducing agent to create spherical gold NPs (AuNPs) with
a diameter of around 25nm. These AuNPs were then combined with keratin in a
1:100 weight ratio, with extra keratin added to guarantee that binding sites were
fully saturated. The resulting solution was shaken overnight, and unbound keratin
was removed by centrifugation and resuspension. To identify Ker-AuNPs within the
3D constructs, they were labeled with FITC, which shows a clear emission at
542nm, conrming successful conjugation. The 3D constructs containing U87-MG
cells and Ker-AuNPs demonstrated enhanced cell proliferation, with cells aligning
along bioprinted bers over time. Importantly, cell proliferation occurred particularly in the presence of Ker-AuNPs, indicating that the NPs did not interfere with
cell proliferation within the supporting biomaterial. Another study by Qin etal. [69]
achieved bacterial outer membrane vesicle-templated biomimetic NPs by using
outer membrane vesicles (OMVs) derived from Escherichia coli Nissle 1917 as
nanoreactors to synthesize biomimetic copper sulde NPs (CuS-OMVs) by introducing copper and sulfur compounds to the OMVs, leading to the growth of CuS
nanocrystals on the OMV template for synergistic photothermo-immunotherapy.
The researchers characterize the resulting CuS-OMVs through various techniques,
such as DLS for size analysis, TEM for morphology observation, and spectroscopy
for absorption measurements. Through this novel approach they overcome limitations associated with traditional PTT agents, such as suboptimal photothermal conversion efciency and inadequate tumor accumulation. Yang etal. [70] produced
DC@BPBBT dots, which are bioinspired aggregation-induced emission (AIE)
nanodots with hitchhiking capability, for improved cancer treatment. Dendritic cell
membranes were applied to nanoaggregates of near-infrared (NIR) AIE polymeric
photothermal agents (BPBBT dots) to form the nanodots, as shown in Fig.4.3a.
These nanodots exhibited strong NIR-II uorescence and efcient photothermal
conversion. The size of the nanodots was characterized using transmission electron
microscopy (TEM) and dynamic light scattering, revealing an average size of
approximately 147.2nm for DC@BPBBT dots and 136nm for BPBBT dots as
shown in Fig.4.3b. When the nanodots were kept at 4°C for 10days, it was discov-
ered that they had high colloidal stability. The addition of DC membranes increased
the nanodot size by around 10 nm due to the membrane wrapping. The zeta

126
Fig. 4.3 Synthesis and characterization of Pt nanomaterial. (a) Synthesis process of NP. (b)TEM
image of NP. (c) Tumor cells treated with DC@BPBBT dots had much lower HSP70 levels. (d)
Intravenous injections, the mice received either DC@BPBBT dots or BPBBT dots. (e) The measurement of tumor’s size every 2days after treatment with DC@BPBBT dots and moderate PTT
(42 °C). (f) Body weight variation after treatment with DC@BPBBT dots and moderate PTT
(42°C). (Reprinted with permission from Wiley [70])
D. Panda etal.
potential was measured at −39.3mV for BPBBT dots and −17.8mV for DC@
BPBBT dots. The composition of membrane proteins from DCs on the nanodots’
surface was analyzed using SDS-PAGE electrophoresis, conrming successful
coating of the NPs with DCs while retaining DC membrane characteristics. This
approach holds promise for improved cancer therapy and drug delivery.
In a study by Li etal. [71], biomimetic NPs were ingeniously crafted for tumor
immuno-PTT. The process involved dissolving indocyanine green (ICG) and
NLG919 (an IDO-1 enzyme inhibitor) in DMSO, and F127in an aqueous solution.
By gently adding the ICG and NLG919 mixture to the F127 solution under ultrasound, self-assembled micelles were born. To perfect these micelles, dialysis was
used to remove unbound drugs and solvents. The next step involved encapsulating
cancer cell membranes. This was achieved by harvesting 4T1 cancer cells, breaking
them open, and combining the resulting cell membrane with the micelles through
extrusion. This resulted in theremarkable biomimetic NPs, known as CFIN.These
NPs were thoroughly examined for size, shape, and charge, revealing an average
size of approximately 220nm, courtesy of the cell membrane coating. Notably, the
zeta potential settled at around −23mV, conrming the successful coating process.
Xiao et al. [72] use top-down synthesis approach of polydopamine-coated gold
nanostars (PDA/GNS@aPD-L1 NPs) with anti-PD-L1 single-chain variable fragment functional cells. The rst step was to create lentivirus particles bearing the
anti-PD-L1 scFv by synthesizing the nucleotide sequences encoding those antibodies. In order to produce stable anti-PD-L1 scFv functional cells (aPD-L1 293T)
under puromycin selection, lentiviral particles were introduced into HEK 293T
cells. Membrane nanovesicles were isolated from aPD-L1 293T cells using

4 Biological Smart Materials: Materials forCancer Treatment
127
differential centrifugation. Then, PDA-GNS (polydopamine-coated gold nanostars)
were synthesized, and a layer of polydopamine was formed on their surface. The
aPD-L1 NVs were coated on the surface of PDA-GNS by co-extrusion through a
polycarbonate membrane. The resulting PDA/GNS@aPD-L1 NPs were characterized by TEM, DLS, and UV-vis spectroscopy to observe their morphology, size, and
surface zeta potential, respectively. The NP size was approximately 200 nm as
shown in Fig.4.4a, b, and the zeta potential was measured at −25.7 ± 0.4 mV
(DMSNs), +6.8 ± 0.7 mV (DMSNs-NH2), −32.4 ± 1.0 mV (DMSNs-COOH),
−14.1±1.2mV (DMSNs3), and −9.4±0.8mV (DMSNs3@HA). These PDA/
GNS@aPD-L1 NPs have potential applications in cancer immunotherapy, particularly for targeting tumor tissues.
4.6 Upconverting NP (UCNP)
The advancement of cancer treatment shows great potential through the development of nanomedicine agents, specically NPs. The ability of NPs to specically
target tumors, efciently deliver drugs, overcome drug resistance, and integrate
diverse approaches to treatment makes them a powerful tool in the ght against
Fig. 4.4 Synthesize and characterization of nanomaterial. (a) TEM image of PDA/GNS@aPD-L1
NPs. (b) Different size of NPs using DLS. (c) Photothermal conversion capability exhibited no
discernible modications. Under 808-nm laser irradiation. (d) The temperature of a PDA/GNS@
aPD-L1 NP solution (0.8mg/mL) quickly climbed to around 54°C within 5min. (e) Photothermal
stability after 10cycles. (f) Photothermal conversion at various concentrations. (g) Power densities
variation. (h) Cell viability using the CCK-8 test. (i) Intravenous injection of drug. (j) Tumor volume. (Reprinted with permission from Elsevier [72])

128
D. Panda etal.
cancer. As research in nanotechnology continues to evolve, we can expect further
advancements in personalized and more efcient cancer therapies. When compared
to other nanomaterials implemented in cancer treatment, upconverting NPs (UCNPs)
possess unique inherent characteristics that make them highly promising for theranostic needs [73]. The process of upconversion (UC) involves the successive
absorption of many photons. Utilizing trivalent lanthanide ions placed in an appropriate inorganic host lattice, which have extended lifetimes and genuine ladder-like
energy levels, allows for the achievement of this phenomena, as a result of this
complex energy level structure, the upconversion process generates higher-energy
anti-stokes luminescence [74]. The upconversion process includes the conversion of
two or more low-energy excitation photons, found in the near-infrared (NIR) light
spectrum into emissions of shorter wavelengths, including NIR, visible, or even
ultraviolet (UV) light. This transformation takes place by utilizing trivalent lanthanide ions that possess unique energy level arrangements. It is essential to acknowledge that upconversion exhibits distinct characteristics compared to nonlinear
multiphoton absorption observed in organic dyes and quantum dots (QDs), where
two or more photons are simultaneously absorbed via virtual states. On the contrary,
the process of upconversion relies on the consecutive absorption of photons in a
progressive manner, resulting in the production of emissions with increased energy
levels [75]. High Efciency and Multicolor Emissions, Monodispersed Small Size,
Uniform Shape and Stoichiometric Composition, Nanochemically Engineered
Surface, Biocompatibility, and NIR Light Excitation are only a few of the essential
characteristics of UCNPs for bio-applications.
4.6.1 Synthesis
Zhao etal. [76], by using the Sol-Gel method, synthesized persistent luminescent
nanocarriers (PLNs) by taking Ca(NO3)2·4H2O, Pr(NO3)3·6H2O and Ti(OC4H9)4 as
a starting material. Ti(OC4H9)4 reacts with nitric acid to form titanyl nitrate, an intermediate compound. Ca(NO3)2·4H2O and Pr(NO3)3·6H2O separately dissolved in titanyl nitrate solution. This formed solution contains calcium, praseodymium, and
titanium ions. Followed by stirring and reaction process, a white precursor material
formed and heated in a mufe furnace at a temperature range of 600–900°C for 3h.
Finally, CaTiO3: 0.1% Pr3+ was formed using a ball grinder and puried by centrifugation. Further, they synthesized upconverting and persistent luminescent nanocarriers (UPLNs) using YbCl3·6H2O, TmCl3·6H2O and synthesized CaTiO3: 0.1%Pr3+
PLNs as a starting material in which TmCl3·6H2O and YbCl3·6H2O were dissolved
in ethanol, followed by 2h of stirring at 50°C.To produce a white precursor, the
resultant mixture was then heated for 3 h at 600–900 °C in a mufe furnace.
Afterward, the UPLNs were then processed for nal preparation by using ball
grinder and centrifuged to remove impurities. Then, using the CTAB template
approach, they synthesized upconverting and persistent luminous nanocarriers
(UPLNs) loaded mesoporous silica NPs (UPLNs@mSiO2), characterized their size

4 Biological Smart Materials: Materials forCancer Treatment
Fig. 4.5 Synthesize and characterization of nanomaterial. (a) TEM image of UPLNs@mSiO2. (b)
The phenomenon of localized heating induces hyperthermia at the tumor site, resulting in the
destruction of tumor tissue and resulting in ow cytometry analysis. (c, d, e) After treatment with
various samples (10g/ml) the tumor weight and volume curve after 30days of treatment with various samples and comparing with control group. (Reprinted with permission from Elsevier [76])
129
using TEM, and found that they possessed excellent monodispersity with an average diameter of 200nm and a very clear prole as shown in Fig4.5a, where UPLNs
water solution was mixed with CTAB water solution and stirred overnight. Keeping
the temperature at 60°C, this UPLNs-CTAB solution was introduced to water, ethanol and 2M NaOH solution in a round bottom ask and left the solution to get stabilized. Following stabilization, TEOS was added, and the reaction continued for
3h. The reaction mixture was then centrifuged and rinsed with ethanol ve times at
a speed of 10,000rpm. For removal of the CTAB template, the resulting product
was suspended in ethanol and processed to a 3-h reaction at 60°C with NH4NO3 in
a round bottom ask. Subsequent centrifugation and ethanol washing were performed to get nal product and the nal product was resuspended in water for later
applications. Furthermore, for treatment applications ICG(%−20mg) was added
into UPLNs@mSiO2 in water. The mixture was centrifuged ve times at an acceleration of 8000rpm after being agitated for 24h at room temperature. The nished
item was then re-dissolved in water for further use. Xing etal. [77] synthesized
OA-coated UCNPs using a mixture of certain chemicals like LuCl3, YbCl3, and
ErCl3 whichwas subjected to heating in a ask with OA and ODE.The aforementioned combination turned into a clear liquid when at elevated or high temperatures,
and then it was cooled down. Additional substances (NaOH and NH4F) were introduced into the mixture and stirred for a short period of time. The liquid underwent
subsequent heating at a very high temperature, followed by natural cooling. After
the liquid cooled down, more alcohol was added to the solution. The mixture was

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D. Panda etal.
then centrifuged, and the particles that formed were separated through the spinning,
extracted out, and subjected to triple alcohol cleaning. Further for synthesizing
polyaniline-coated UCNPs (UCNPs-PANPs) initially, the coated UCNPs underwent a transformation process to become bare UCNPs by using a ligand-free
approach. The experiment procedure involved the addition of OA-coated UCNPs
into a ask containing an excess solution of NOBF4. The mixture got dispersed
through the application of sonication for 10min and then separated by spinning
within a centrifuge. The in-situ oxidative polymerization process was used for the
formation of UCNPs-PANPs. To achieve this, bare UCNPs were introduced into a
solution including sodium do-decyl benzene sulfonate and polyvinyl alcohol. The
mixture was made homogenous through ultrasonic treatment. Then, after a 30-min
period of stirring, a small volume of aniline monomer was added. Following the
additional duration of 30min of stirring, (NH4)2S2O8 was incorporated into the mixture to commence the polymerization reaction. The mixture was subjected to a
polymerization process for 5h at room temperature, resulting in the formation of
UCNPs-PANPs exhibiting a visually dark-blue precipitate.
4.7 Inorganic NP
Two-dimensional (2D) nanostructures have attracted a lot of attention in the modern
period in a variety of scientic elds, including biomedical devices, nano- biosensors,
nanomedicine, bio-membranes, and energy storage devices [78]. This enthusiasm
stems from their exceptional physicochemical properties, notably their high surfaceto- volume ratio, ultrathin nature, customizable surface modications, and rapid
conjugation with biomolecules [79]. Recent efforts in designing and synthesizing
2D inorganic nanostructures have unveiled a promising avenue for cancer therapy
and potential breakthroughs in non-invasive treatments. Nano-graphene (graphene
oxide), black phosphorous (BP), MXenes (carbides and nitrides), and transition
metal dichalcogenides (TMDCs) are only a few of the sophisticated 2D-functional
nanomaterials described as prominent contenders, capturing attention for their easily adjustable physicochemical attributes [80]. Silica NPs are known for their biocompatibility and versatility. They can be engineered to encapsulate drugs,
enhancing their stability and enabling controlled release at tumor sites. By modifying the surface of silica NPs with targeting ligands, we can ensure that these NPs
specically accumulate in cancer cells, minimizing impact on healthy tissues. This
targeted drug delivery approach improves treatment efcacy and reduces side
effects [81]. Carbon nanotubes (CNTs) possess unique thermal and optical properties. They can absorb light across a wide range of wavelengths, including nearinfrared light, making them suitable for PTT. CNTs can accumulate in tumors and,
upon exposure to light, convert the absorbed energy into heat, leading to cancer cell
destruction. Additionally, CNTs can be functionalized with drugs and targeting
molecules, enabling precise delivery of therapeutic agents to the tumor site [82].
Quantum dots (QDs), semiconductor nanocrystals, have tunable optical properties

4 Biological Smart Materials: Materials forCancer Treatment
131
that make them valuable for imaging and therapy. They emit light at specic wavelengths when excited, allowing for accurate imaging of tumor sites [83]. Moreover,
QDs can be conjugated with drugs, enabling targeted therapy as the QDs accumulate in cancer cells and release the therapeutic payload. Particularly in the realm of
modern imaging-guided cancer therapy, these materials have gained traction. This
chapter delves into the ongoing advancements in crafting 2D inorganic nanosheets,
their synthesis approach, and their prospective applications in PTT and integrated
cancer theranostics [84].
4.7.1 Synthesis
Cheng etal. [85] synthesized PEGylated WS2 nanosheets and investigated their
potential as a multifunctional theranostic agent for cancer therapy. The synthesis
process of WS2 nanosheets involved immersing 100mg of WS2 powder in 3ml of
n-butyllithium (1.6M in hexane) and stirring for 48h in a vacuum glove box. The
resulting mixture was ltered, rinsed with hexane, and then suspended in distilled
water using sonication to achieve exfoliation. The WS2 nanosheets were subsequently centrifuged, washed, and dialyzed to remove any residual ions. The WS2
nanosheets were then surface-modied with mPEG-LA polymer. For this, mPEG NH2 was reacted with lipoic acid (LA) in dichloromethane to yield LA-PEG.The
WS2 nanosheets were dispersed in water and mixed with LA-PEG, followed by
sonication and centrifugation to remove excess LA-PEG.The nal product, WS2PEG, was suspended in distilled water. The properties of the synthesized WS2-PEG
nanosheets were characterized. Figure4.6a depicts the schematic representation of
the synthesis and modication process. It shows the functionalization of the WS2
nanosheets with LA-PEG through a W-S bond. This functionalization is crucial for
enhancing the stability and biocompatibility of the nanosheets, Fig.4.6b illustrates
the stability of the WS2-PEG in different physiological solutions and shows how the
WS2-PEG nanosheets maintain their individual dispersion in various solutions over
time, highlighting their enhanced stability compared to the original WS2 nanosheets.
Figure4.6c depicts the graph showing the average thickness of WS2 nanosheets
compared to PEGylated WS2 nanosheets and increase in thickness indicates successful PEGylation. Figure4.6d represents the results of CT imaging of mice with
4T1 tumors after intratumoral (i.t.) injection of WS2-PEG nanosheets and shows the
tumor with enhanced contrast, where the Hounseld Unit (HU) value increased
signicantly after the injection of WS2-PEG nanosheets. This increased contrast
indicates the ability of the nanosheets to serve as a contrast agent for CT imaging.
Figure4.6e shows CT images of mice with 4T1 tumors after intravenous (i.v.) injection of WS2-PEG nanosheets. The CT images taken 24h after injection would
reveal enhanced contrast in the tumor area, as indicated by an increase in HU values. Additionally, the liver might show enhanced contrast, suggesting uptake of the
nanosheets by the reticuloendothelial system (RES). This nding supports the use

132
Fig. 4.6 Synthesize and characterization of WS2-PEG nanosheets. (a) Schematic representation
of the synthesis and modication process. (b) Stability of the WS2-PEG in different physiological
solutions. (c) Thickness of WS2 nanosheets compared to PEGylated WS2 nanosheets. (d) CT
imaging of mice with 4T1 tumors after intratumoral (i.t.) injection of WS2-PEG nanosheets shows
the tumor with enhanced contrast. (e) CT images of mice with 4T1 tumors after intravenous (i.v.)
injection of WS2-PEG nanosheets. (f) The photoacoustic imaging tomography (PAT) outcomes on
a mouse model with 4T1 tumors are presented. (g) Contrast is drawn between the absolute photoacoustic signals within tumors originating from mice subjected to i.t. injection and i.v. injection of
WS2-PEG nanosheets. (h) Temperature changes in the tumor region due to different treatment
strategies. (i) Quantitative comparison of tumor growth. (j) Regression of tumors in WS2-PEGtreated mice after PTT. (Reprinted with permission from Wiley [86])
D. Panda etal.
of WS2-PEG nanosheets as a promising contrast agent for CT imaging after systemic administration.
Huang etal. [86] create a new theranostic platform employing biodegradable
plasmonic gold nanovesicles (BGVs) for improved cancer imaging and therapy.
With the use of a PEG-b-PCL block copolymer with a disulde link, they developed
a special assembly method that allowed for the dense packing of gold nanoparticles
(GNPs) with certain orientations, creating an extremely potent plasmonic coupling
effect between nearby GNPs. Strong NIR absorption, resulting from this coupling
effect, was necessary for effective PTT. The BGVs displayed outstanding qualities,
such as a high photothermal conversion efciency (37%), the capacity to discretely
form GNPs at high temperatures, simultaneous thermal/photoacoustic imaging
(PAI), and improved PTT effectiveness. Additionally, after the conclusion of the
PTT, the BGVs showed increased clearance of dissociated particles. The BGVs
showed excellent solubility, aqueous medium stability, and biocompatibility, making them interesting candidates for biological applications. The PEG-b-PCL block
copolymer played a key role in the synthesis of BGVs, which the researchers
described in detail. They also highlighted the amazing features of these molecules,
emphasizing their potential for cancer imaging and treatment. Figure4.7a depicts a
schematic representation of the proposed design of the biodegradable BGVs composed of poly(ethylene glycol)-b-poly(e-caprolactone) (PEG-b-PCL)-tethered
GNPs for effective cancer imaging and treatment through improved PTT efcacy,
simultaneous thermal/PA imaging, and biodegradability. This effect allowed the
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