Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_151_библиотеки_им_акад_М_И_Перельмана
.pdf
266 A. Mousavi et al.
https://t.me/med1917
Mackall CL, Miklos DB (2017) CNS endothelial cell activation emerges as a driver of CAR T cell–
associated neurotoxicity. Cancer Discov 7:1371–1373
Maharaj AD, Holland JF, Scarborough RO, Evans SM, Ioannou LJ, Brown W, Croagh DG, Pilgrim
CHC, Kench JG, Lipton LR, Leong T, McNeil JJ, Nikfarjam M, Aly A, Burton PR, Cashin PA,
Chu J, Duong CP, Evans P, Goldstein D, Haydon A, Hii MW, Knowles BPF, Merrett ND,
Michael M, Neale RE, Philip J, Porter IWT, Smith M, Spillane J, Tagkalidis PP, Zalcberg JR
(2019) The upper gastrointestinal cancer registry (UGICR): a clinical quality registry to monitor
and improve care in upper gastrointestinal cancers. BMJ Open 9:e031434–e031434
Majzner RG, Mackall CL (2018) Tumor antigen escape from CAR T-cell therapy. Cancer Discov
8:1219–1226
Mansfield PF (2011) Clinical features, diagnosis, and staging of gastric cancer. Last literature
review: May
McClellan JL, Davis JM, Steiner JL, Enos RT, Jung SH, Carson JA, Pena MM, Carnevale KA,
Berger FG, Murphy EA (2012) Linking tumor-associated macrophages, inflammation, and
intestinal tumorigenesis: role of MCP-1. Am J Physiol Gastrointest Liver Physiol 303:
G1087–G1095
Mellman I, Coukos G, Dranoff G (2011) Cancer immunotherapy comes of age. Nature 480:
480–489
Murad JP, Tilakawardane D, Park AK, Lopez LS, Young CA, Gibson J, Yamaguchi Y, Lee HJ,
Kennewick KT, Gittins BJ, Chang W-C, Tran CP, Martinez C, Wu AM, Reiter RE, Dorff TB,
Forman SJ, Priceman SJ (2021) Pre-conditioning modifies the TME to enhance solid tumor
CAR T cell efficacy and endogenous protective immunity. Mol Ther 29:2335–2349
Nie Y, Lu W, Chen D, Tu H, Guo Z, Zhou X, Li M, Tu S, Li Y (2020) Mechanisms underlying
CD19-positive ALL relapse after anti-CD19 CAR T cell therapy and associated strategies.
Biomarker Res 8:18
Pantano F, Berti P, Guida FM, Perrone G, Vincenzi B, Amato MMC, Righi D, Dell'Aquila E,
Graziano F, Catalano V, Caricato M, Rizzo S, Muda AO, Russo A, Tonini G, Santini D (2013)
The role of macrophages polarization in predicting prognosis of radically resected gastric cancer
patients. J Cell Mol Med 17:1415–1421
Peng Y-P, Zhu Y, Zhang J-J, Xu Z-K, Qian Z-Y, Dai C-C, Jiang K-R, Wu J-L, Gao W-T, Li Q,
Du Q, Miao Y (2013) Comprehensive analysis of the percentage of surface receptors and
cytotoxic granules positive natural killer cells in patients with pancreatic cancer, gastric cancer,
and colorectal cancer. J Transl Med 11:262
Posey AD Jr, Schwab RD, Boesteanu AC, Steentoft C, Mandel U, Engels B, Stone JD, Madsen TD,
Schreiber K, Haines KM, Cogdill AP, Chen TJ, Song D, Scholler J, Kranz DM, Feldman MD,
Young R, Keith B, Schreiber H, Clausen H, Johnson LA, June CH (2016) Engineered CAR
T cells targeting the cancer-associated Tn-Glycoform of the membrane mucin MUC1 control
adenocarcinoma. Immunity 44:1444–1454
Rahma OE, Khleif SN (2011) Therapeutic vaccines for gastrointestinal cancers. Gastroenterol
Hepatol 7:517–564
Raj D, Nikolaidi M, Garces I, Lorizio D, Castro NM, Caiafa SG, Moore K, Brown NF, Kocher HM,
Duan X, Nelson BH, Lemoine NR, Marshall JF (2021) CEACAM7 is an effective target for
CAR T-cell therapy of pancreatic ductal adenocarcinoma. Clin Cancer Res 27:1538–1552
Sadelain M, Brentjens R, Rivière I (2013) The basic principles of chimeric antigen receptor design.
Cancer Discov 3:388–398
Santomasso BD, Park JH, Salloum D, Riviere I, Flynn J, Mead E, Halton E, Wang X, Senechal B,
Purdon T (2018) Clinical and biological correlates of neurotoxicity associated with CAR T-cell
therapy in patients with B-cell acute lymphoblastic leukemia. Cancer Discov 8:958–971
Shah AB, Sommerer KR, Almhanna K (2019) Immune checkpoint inhibitors in gastrointestinal
malignancies: what can we learn from experience with other tumors? Trans Gastroenterol
Hepatol 4:73–73
Siddiqui RS, Sardar M (2021) A systematic review of the role of chimeric antigen receptor
T (CAR-T) cell therapy in the treatment of solid tumors. Cureus 13:e14494
Immunotherapy in Gastrointestinal Cancer Focusing on CAR-T Cell Therapy 267
https://t.me/med1917
Siegel RL, Miller KD, Fuchs HE, Jemal A (2021) Cancer statistics, 2021. CA Cancer J Clin
71:7–33
Song Y, Tong C, Wang Y, Gao Y, Dai H, Guo Y, Zhao X, Wang Y, Wang Z, Han W, Chen L
(2018) Effective and persistent antitumor activity of HER2-directed CAR-T cells against gastric
cancer cells in vitro and xenotransplanted tumors in vivo. Protein Cell 9:867–878
Staudt RE, Carlson RD, Snook AE (2022) Targeting gastrointestinal cancers with chimeric antigen
receptor (CAR)-T cell therapy. Cancer Biol Ther 23:127–133
Supimon K, Sangsuwannukul T, Sujjitjoon J, Phanthaphol N, Chieochansin T, Poungvarin N,
Wongkham S, Junking M, Yenchitsomanus PT (2021) Anti-mucin 1 chimeric antigen receptor
T cells for adoptive T cell therapy of cholangiocarcinoma. Sci Rep 11:6276
Thistlethwaite FC, Gilham DE, Guest RD, Rothwell DG, Pillai M, Burt DJ, Byatte AJ, Kirillova N,
Valle JW, Sharma SK, Chester KA, Westwood NB, Halford SER, Nabarro S, Wan S, Austin E,
Hawkins RE (2017a) The clinical efficacy of first-generation carcinoembryonic antigen
(CEACAM5)-specific CAR T cells is limited by poor persistence and transient pre-
conditioning-dependent respiratory toxicity. Cancer 66:1425–1436
Thistlethwaite FC, Gilham DE, Guest RD, Rothwell DG, Pillai M, Burt DJ, Byatte AJ, Kirillova N,
Valle JW, Sharma SK, Chester KA, Westwood NB, Halford SER, Nabarro S, Wan S, Austin E,
Hawkins RE (2017b) The clinical efficacy of first-generation carcinoembryonic antigen
(CEACAM5)-specific CAR T cells is limited by poor persistence and transient pre-
conditioning-dependent respiratory toxicity. Cancer Immunol Immunother 66:1425–1436
Tokhanbigli S, Asadirad A, Baghaei K, Piccin A, Yarian F, Parsamanesh G, Hashemi SM,
Asadzadeh Aghdaei H, Zali MR (2020) Dendritic cell-based therapy using LY6E peptide
with a putative role against colorectal cancer. Immuno Targets Ther 9:95–104
Umut Ö, Gottschlich A, Endres S, Kobold S (2021) CAR T cell therapy in solid tumors: a short
review. Memo Magazine Eur Med Oncol 14:143–149
van Herk EH, Te Velde AA (2016) Treg subsets in inflammatory bowel disease and colorectal
carcinoma: characteristics, role, and therapeutic targets. J Gastroenterol Hepatol 31:1393–1404
Wang R, Xiang S, Feng Y, Srinivas S, Zhang Y, Lin M, Wang S (2013) Engineering production of
functional scFv antibody in E coli by co-expressing the molecule chaperone Skp. Front Cell
Infect Microbiol 3:72
Wang X-T, Kong F-B, Mai W, Li L, Pang L-M (2016) MUC1 Immunohistochemical expression as
a prognostic factor in gastric cancer: meta-analysis. Dis Markers 2016:9421571
Wu J, Chen J, Feng Y, Zhang S, Lin L, Guo Z, Sun P, Xu C, Tian H, Chen X (2020) An immune
cocktail therapy to realize multiple boosting of the cancer-immunity cycle by combination of
drug/gene delivery nanoparticles. Sci Adv 6:eabc7828
Xu J-M, Zhang Y, Jia R, Wang Y, Liu R, Zhang G, Zhao C, Zhang Y, Zou J, Wang Q (2018) Anti-
programmed death-1 antibody SHR-1210 (S) combined with apatinib (a) for advanced hepato-
cellular carcinoma (HCC), gastric cancer (GC) or esophagogastric junction (EGJ) cancer
refractory to standard therapy: a phase 1 trial. J Clin Oncol 36:4075–4075
Yang L, Wang Y, Wang H (2019) Use of immunotherapy in the treatment of gastric cancer. Oncol
Lett 18:5681–5690
Yang Y, McCloskey JE, Yang H, Puc J, Gallegos AAG, Vedvyas Y, Min IM, von Hofe E, Jin MM
(2020) Abstract 6598: eradication of EpCAM expressing solid tumors by low-affinity CAR
T cells. Cancer Res 80:6598–6598
Yang Y, McCloskey JE, Yang H, Puc J, Alcaina Y, Vedvyas Y, Gomez Gallegos AA, Ortiz-
Sánchez E, de Stanchina E, Min IM, von Hofe E, Jin MM (2021) Bispecific CAR T cells against
EpCAM and inducible ICAM-1 overcome antigen heterogeneity and generate superior
antitumor responses. Cancer Immunol Res 9:1158–1174
Yazdanifar M, Zhou R, Grover P, Williams C, Bose M, Moore LJ, Wu ST, Maher J, Dreau D,
Mukherjee AP (2019) Overcoming immunological resistance enhances the efficacy of a novel
anti-tMUC1-CAR T cell treatment against pancreatic ductal adenocarcinoma. Cell 8
Yu S, Yi M, Qin S, Wu K (2019) Next generation chimeric antigen receptor T cells: safety strategies
to overcome toxicity. Mol Cancer 18:125
268 A. Mousavi et al.
https://t.me/med1917
Yu F, Wang X, Shi H, Jiang M, Xu J, Sun M, Xu Q, Addai FP, Shi H, Gu J, Zhou Y, Liu L (2021)
Development of chimeric antigen receptor-modified T cells for the treatment of esophageal
cancer. Tumori 107:341–352
Zeng D, Wu J, Luo H, Li Y, Xiao J, Peng J, Ye Z, Zhou R, Yu Y, Wang G, Huang N, Wu J, Rong X,
Sun L, Sun H, Qiu W, Xue Y, Bin J, Liao Y, Li N, Shi M, Kim K-M, Liao W (2021) Tumor
microenvironment evaluation promotes precise checkpoint immunotherapy of advanced gastric
cancer. J Immunother Cancer 9:e002467
Zhai X, You F, Xiang S, Jiang L, Chen D, Li Y, Fan S, Han Z, Zhang T, An G, Zhang B, Chen Y,
Meng H, Yang L (2021) MUC1-Tn-targeting chimeric antigen receptor-modified Vγ9Vδ2
T cells with enhanced antigen-specific anti-tumor activity. Am J Cancer Res 11:79–91
Zhang Q, Zhang Z, Peng M, Fu S, Xue Z, Zhang R (2016) CAR-T cell therapy in gastrointestinal
tumors and hepatic carcinoma: from bench to bedside. OncoImmunology 5:e1251539
Zhang C, Wang Z, Yang Z, Wang M, Li S, Li Y, Zhang R, Xiong Z, Wei Z, Shen J, Luo Y,
Zhang Q, Liu L, Qin H, Liu W, Wu F, Chen W, Pan F, Zhang X, Bie P, Liang H, Pecher G, Qian
C (2017) Phase I escalating-dose trial of CAR-T therapy targeting CEA(+) metastatic colorectal
cancers. Mol Ther 25:1248–1258
Zhang E, Yang P, Gu J, Wu H, Chi X, Liu C, Wang Y, Xue J, Qi W, Sun Q, Zhang S, Hu J, Xu H
(2018a) Recombination of a dual-CAR-modified T lymphocyte to accurately eliminate pancre-
atic malignancy. J Hematol Oncol 11:102
Zhang Q, Zhang H, Ding J, Liu H, Li H, Li H, Lu M, Miao Y, Li L, Zheng J (2018b) Combination
therapy with EpCAM-CAR-NK-92 cells and Regorafenib against human colorectal cancer
models. J Immunol Res 2018:4263520
Zhang BL, Li D, Gong YL, Huang Y, Qin DY, Jiang L, Liang X, Yang X, Gou HF, Wang YS, Wei
YQ, Wang W (2019a) Preclinical evaluation of chimeric antigen receptor-modified T cells
specific to epithelial cell adhesion molecule for treating colorectal cancer. Hum Gene Ther
30:402–412
Zhang Y, Xu J, Zhang N, Chen M, Wang H, Zhu D (2019b) Targeting the tumour immune
microenvironment for cancer therapy in human gastrointestinal malignancies. Cancer Lett
458:123–135
Zhang H, Zhao H, He X, Xi F, Liu J (2020) JAK-STAT domain enhanced MUC1-CAR-T cells
induced esophageal cancer elimination. Cancer Manag Res 12:9813–9824
Zhou Y, Wen P, Li M, Li Y, Li XA (2019) Construction of chimeric antigen receptor-modifi ed
T cells targeting EpCAM and assessment of their anti-tumor effect on cancer cells. Mol Med
Rep 20:2355–2364
1Development of Biocompatible
https://t.me/med1917
2Nanocarriers for the Treatment
3of Colorectal Cancer
4Bibi Noorheen Haleema Mooneerah Neeroa,
5Nurshafida Adzlin Shamsul Anuar, Brianna, Mostafa Yusefi,
6Kamyar Shameli, and Sin-Yeang Teow
Abstract
B. N. H. M. Neeroa · N. A. S. Anuar · Brianna
Department of Medical Sciences, School of Medical and Life Sciences, Sunway University,
Selangor, Malaysia
M. Yusefi
Malaysia-Japan International Institute of Technology, Universiti Teknologi Malaysia, Kuala
Lumpur, Malaysia
Institute of Biological Sciences, Faculty of Science, Universiti Malaya, Kuala Lumpur, Malaysia
K. Shameli
School of Medicine, Institute of Virology, Technical University of Munich, Munich, Germany
S.-Y. Teow (
✉)
Department of Biology, College of Science, Mathematics and Technology, Wenzhou-Kean
University, Wenzhou, China
e-mail: tyeang@kean.edu
7
8Colorectal cancer is one of the top three cancers with highest incidence in the
9world. Therapies using medication remain one of the common treatment methods,
10but the treatment efficacy is often hindered by inefficient tumour penetration and
11drug delivery. Hence, the development of drug nanocarrier is becoming more
12important in order to maximise the drug delivery to the target cells and the cancer-
13killing capacity. In recent years, the use of nanoparticles for cancer therapy has
14gained traction due to their diverse characteristics and high flexibility for
15modifications. While exerting anticancer action when used individually,
16nanoparticles are also suitable to be used as a delivery system to transport the
17anticancer drug to the targets. In order to develop a non-toxic nanoparticles-based
18drug carrier, various biomaterials such as chitosan, xanthan gum, cellulose and
19alginate are also used to enhance the biocompatibility of the nanocarrier. This
20chapter discusses the recent development of biomaterial-derived nanocarriers and
21their use towards colorectal cancer therapy. Some challenges and limitations are
#
The Author(s), under exclusive license to Springer Nature Switzerland AG 2023
Interdisciplinary Cancer Research, https://doi.org/10.1007/16833_2023_158
Published online: 6 April 2023
269
270 B. N. H. M. Neeroa et al.
https://t.me/med1917
22 also discussed here to provide insights for future development of biocompatible
23 drug nanocarriers.
24
25 Biomaterial · Colorectal cancer · Nanocarrier · Nanomedicine · Treatment
26 1 Introduction
27 1.1 Colorectal Cancer and Its Management
28 Colorec tal cancer is the third most diagnosed cancer and the third leading cause
29 of cancer death both in men and women worldwide. An estimated number of
30 1.8 million people were newly diagnosed with CRC, and 0.9 million people died
31 from the disease in 2020 (Xi and Xu 2021). Generally, the colon epithelial tissues are
32 genetically altered to form cancerous polyps which accumulate and develop into
33 cancer (Bray et al. 2018). Patients with CRC can be treated by surgery, radiation
34 therapy, chemotherapy, targeted therapy, immunotherapy or in combination
35 according to their medical conditions. However, each treatment option may come
36 with possible side effects (Biller and Schrag 2021). As this chapter focuses on the
37 development of drug nanocarrier, we will focus on the therapies using medication
38 which include chemotherapy, targeted therapy and immunotherapy.
39 Chemotherapy is the use of anticancer drugs to destroy fast-growing cells,
40 inhibit ing the growth or division of cancer cells. According to cancer.org, patients
41 often receive several cycles of treatment either consisting of one type of drug or more
42 over a period of time. Some of the commonly used drugs include 5-fluorouracil
43 (5-FU), capecitabine (Xeloda), irinotecan (Camptosar) and oxaliplatin (Eloxatin).
44 They can also be used in combination such as FOLFOX (5-FU with leucovorin
45 and oxaliplatin), FOLFIRI (5-FU with leucovorin and irinotecan), XELIRI/
46 CAPIRI (capecitabine with iri notecan) and XELOX/CAPEOX (capecitabine with
47 oxalip latin) (Biller and Schrag 2021). The two common method of administering the
48 drug is either via systemic chemotherapy, where the drug is administered intrave-
49 nously or orally and travels to almost all areas of the body, or regional chemother-
50 apy, where the drug is administered into the artery which directs to a specific part of
51 the body with cancer.
52 Targeted therapy is a treatment that targets specific gene or prote in or even the
53 tumou r ‘microenvironment’ that contributes to cancer growth, to prevent the cancer
54 cells from spreading to surrounding healthy cells. Some of these drugs such as
55 bevacizumab, regorafenib, ramucirumab and ziv-aflibercept are designed to inhibit
56 angiogenesis while others such as cetuximab and panitumumab are designed to
57 block cell receptors such as epidermal growth factor receptor (EGFR). Often, these
58 drugs are also used in combination with drugs in chemotherapy to maximise the
59 treatment efficacy. As these drugs act specifically on the target, cells cannot respond
60 to the drugs if the tumour cells have specific mutations on the target such as EGFR,
Keywords
Development of Biocompatible Nanocarriers for the Treatment of Colorectal Cancer 271
https://t.me/med1917
61RAS and BRAF mutations, hence rendering the therapy ineffective (Awi et al. 2021;
62Pang et al. 2019). Immunotherapy, on the other hand, is designed to boost the body’s
63immune response to kill the cancer cells. Examples of drugs include pembrolizumab,
64nivolumab, dostarlimab and ipilimumab. Similarly, these drugs can also be used
65along with chemotherapeutic drugs such as capecitabine, 5-FU, oxaliplatin and
66irinotecan to maximise the treatment outcome (Xie et al. 2020).
671.2 Limitations of Medication-Based Therapies Against CRC
68In addition to the toxicity of chemotherapeutic drugs that limit the dosage and
69frequency of treatment, tumour-penetrating capacity, tissue distribution, stability
70and bioavailability of the drugs also play important roles in determining the success
71of the cancer therapy. While acting as the main component of tumour microenviron-
72ment, tumour is also surrounded by non-cancer or stromal cells such as fibroblasts,
73immune cells, mesenchymal stem cells as well as various types of extracellular
74matrix (ECM) (Gallo et al. 2021). These components also play important roles in
75supporting the growth and progression of the tumours and have also been identified
76as one of the major obstacles that complicate and resist cancer treatment. Some of the
77mechanisms include serving as a multilayer physical barrier enriched with the ECM
78to block drug penetration and the drug targets as well as directing the soluble
79mediators such as cytokines and chemokines to block the treatment (Gallo et al.
802021). This poses a huge challenge especially for those large-sized drugs with weak
81tissue-penetrating capacity.
82Next, the convent ional chemotherapeutic drugs such as 5-FU which is a non-
83target-specific drug can be further affected by the stromal cells. Due to the tissue
84architecture within the tumour, the drug may not be successfully delivered to the
85tumour sites and only retain at certain nonspecific sites, this may then give rise to
86another issue which is off-target toxicity. In another scenario, drugs that reach the
87tumour sites have to translocate through the interstitial space to reach their target
88cells, but this may be blocke d by the endothelial cell layer which lines the blood
89vessels, render ing the failure of drug delivery. However, it has been known that the
90endothelial cell layers are rather poorly aligned in the tumour sites, hence resulting
91in the ‘leaky’ capillaries to allow the transendothelial transport of drugs. Under
92intratumoural pressure, the condition surrounding the tumour is often hypoxic and
93highly acidic due to the low availability of oxygen and accumulation of lactic acids
94(Gallo et al. 2021). This may affect the cellular uptake and the tissue distribution of
95the drug. The low pH condition may also affect the stability of the drug at the tumour
96site, and hence resulting in the reduced tumour-killing action.
97Aside from the ones stated above, the drugs commonly used for cancer therapy
98are inefficient in eradicating cancer cells as they often exhibit poor water solubility,
99inefficient biodistribution, and are hydrophobic (Choukaife et al. 2022). This,
100in turn, will prompt the need to increase the frequency of therapy and dosage
101requirement, which subsequently will lead to devastating adverse side effects.
102To summarise, conventional anticancer drugs have so far demonstrated certain
103limitations which impede the success rate of the therapy.
272 B. N. H. M. Neeroa et al.
https://t.me/med1917
104 2 Development of Nanocarriers Against Cancer
105 2.1 Properties of Nanocarriers
106 As highlighted in the previous section, several issues with the conventional
107 drug delivery method can be improved using various types of nanomedicine.
108 Nanomedicine is the application of nanomaterials or nanoparticles which are about
109 1–100 nm to medicine. According to de SL Oliveira et al. (2021), nanoparticles
110 (NPs) are classified as complex molecules which can be functionalised with different
111 types of cores (chemical materials), elements (surfactants or ions) and/or nuclei
112 (central portion). This rich surface chemistry allows for various surface
113 modifications including to make them pH-, temperature-, stimuli-responsive, enable
114 drug and cargo loading as well as the flexibility which enables size and shape
115 modifications. These flexibilities could partly tackle the challenges of conventional
116 drug therapy, either via enhancing absorption and tumour penetration or stabilising
117 drug formulation. For example, the smaller NPs are known to effectively permeate
118 the tumour and hence kill the cancer cells more potently. The possible modifications
119 of nanoparticles could also be conjugated with anticancer drugs, serving as a drug
120 nanocarrier to make the drug more stable and effective under the stringent tumour
121 microenvironment. They are highly attractive for drugs that have poor water solu-
122 bility and pharmacokinetics and cause severe side effects. These properties make NP
123 a strong candidate as nanocarriers in the drug delivery system (DDS) for treating
124 cancer (Pushpamalar et al. 2021; Neerooa et al. 2021).
125 2.2 Types of Nanocarriers
126 To date, there are various types of nanocarriers that can be used for cancer treat ment
127 and they each have various ways to formulate them. Generally, however, the
128 nanostructure of the NPs is associated with the active drugs. The type of materials
129 to synthesise these nanocarriers can be categorised into two: organic (e.g.,
130 lipid-based, polymer-based) and inorganic (e.g., metal, quantum, nanotube, silica)
131 (Fig. 1). Hybrid nanocarriers, on the other hand, contain a mixture of organic and/or
132 inorganic to receive the benefits of both materials (de SL Oliveira et al. 2021).
133 2.2.1 Organic Nanoparticles
134 Lipid-based nanoparticles (LNPs) constitute a diverse group of nanoparticles that are
135 created from the lipid bilayers, and they often consist of the addition of amphiphilic
136 lipids to water or other hydrophilic liquids. This allows for the encapsulation of both
137 hydrophilic and hydrophobic drug molecules to be either dissolved in the liquid
138 or lipid solution to form NPs (García-Pinel et al. 2019). They demonstrate low rate of
139 toxicity, can control the release of drugs and increase the drug half-life. To date,
140 liposomes, solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs)
141 are the few LNPs that garnered the most attention in the drug discovery of cancer
142 treatment.
Development of Biocompatible Nanocarriers for the Treatment of Colorectal Cancer 273
https://t.me/med1917
Fig. 1 Illustration of the two big categories of NPs, organic or inorganic. They are classified in
accordance with the type of material used in their formation. They offer excellent potential to act as
DDS for colorectal cancer
143Liposome is one of the most extensively studied lipid-based nanoparticles as
144DDS due to its biodegradability and biocompatibility behaviour. They are also
145capable of decreasing the toxicity of anticancer agents while also improving the
146efficacy of their anti-tumour properties (Yingchoncharoen et al. 2016). Various
147methods can be used to generate liposomal NPs which include sonication, extrusion,
148reverse-phase evaporation and solvent injection. Micelles (which can be made up of
149either lipids or polymer) are composed of an amphiphilic lipid head and a hydropho-
150bic single-tail region, forming a micellar nanostructure via supramole cular self-
151assembly. The hydrophilic shell plays an important role in supporting and stabilising
152the hydrophobic core, which carries and protects the drug in an aqueous solution
153(Galetti et al. 2019; Mkam Tsengam et al. 2022; Yadav et al. 2019).
154SLN is a relatively new formulated colloidal nanocarrier which mainly constitutes
155physiological lipids, ranging between 50 and 1,000 nm, and exists as a solid at both
156room and body temperature (García-Pinel et al. 2019). These lipids, namely fatty
157acids, and simple and complex glyceride mixtures are used to form the matrix of
158drug enca psulation, which is stabilised by polymers or surfactants. Development of
159SLNs as a DDS, however, poses some challenges due to their modest drug expulsion
160and loading capacity as crystallisation occurs during storage (Rajabi and Mousa
1612016).
162Therefore, nanostructu red-lipid carrier (NLC) was formulated to tackle the
163limitations of SLNs, making it a second-generation LNP (Chauhan et al. 2020).
164Constituting both solid and liquid lipids, it is typically composed of glyceryl
274 B. N. H. M. Neeroa et al.
https://t.me/med1917
165 dioleate, ethyl oleate, isopropyl myristate or glyceryl tricaprylate (Naseri et al.
166 2015). Besides having a higher drug loading capacity, the liquid lipids in the NLC
167 improve the formulation stability by preventing lipids from crystallising which stops
168 the drug from expulsing during storage (Scioli Montoto et al. 2020).
169 Polymeric nanoparticles (PNPs) have attracted significant attention when studies
170 have exhibited improved drug efficacy by minimising the side effects of anticancer
171 drugs and making these drugs more site-specific (Haider et al. 2022). PNPs are
172 formed when monomers or polymers are polymerised into solid colloidal systems
173 that encapsulate the drug. Their shape and size are highly dependent on the prepara-
174 tion method. Being stable, biocompatible and cheap with low toxicity trait, they
175 are one of the most used systems for drug delivery. PNPs are further divided in
176 accordance with their structural features and formulation process. Ones commonly
177 studied for DDS are nanogels, polymersomes, dendrimers, polymeric micelles and
178 nanocapsules (Haider et al. 2022).
179 Nanogels, also known as hydrogels, are NPs made up of cross-linked network of
180 different water-soluble polymers that can retain large amount of water. Due to its
181 high degree of fluid retention, which resembles biological tissues, nanogel is well
182 known for its high biocompatibility for cancer treatment (Haider et al. 2022).
183 Polymersomes, made of amphiphilic po lymer, mimic the physical properties of
184 liposomes, in which they both are composed of a hydrophilic head with a hydropho-
185 bic bilayer core, and can self-assemble into vesicles (Rideau et al. 2018). Their main
186 role as a nanocarrier is to encapsulate and protect the anticancer drug. Dendrimers
187 are three-dimensional (3D) PNPs that are made up of branched monomers with
188 symmetrical layers surrounding their central core (Brar et al. 2021). Its central core is
189 a spherical structure made of repeating carbon elements with repeating units
190 branching from the central core. The free space within its 3D structure was though t
191 to mediate the encapsulation of drugs of its most studied clinical applications is
192 increasing the solubility of poorly soluble drugs (Sherje et al. 2018).
193 PNPs can also self-assemble into biphasic spherical structures, such as
194 nanocapsules, which are generally formed with a core (inner material) and a shell
195 (outer layer) (Ghosh Chaudhuri and Paria 2012). It is important to note that most
196 of these nanocarriers despite being synthesised from different materials can be
197 modified to carry drugs or other cargoes that could target and kill cancer cells.
198 These PNPs are typically made up of synthetic polymers via synthetic methods
199 such as nanoprecipitation, electrospray, emulsification and particle replication in
200 nonwetting templates (PRINT).
201 2.2.2 Inorganic Nanoparticles
202 Among the metal NPs, the well-characterised and most studied NPs are gold and
203 silver NPs. One of the attractive properties of gold NPs is their photothermal
204 properties which are suitable for cancer treatment. When used together with a
205 laser, the gold nanoparticles or the loaded drugs can be released in a controlled
206 manner to specifically target and kill tumour cell s without inducing nonspecific
Development of Biocompatible Nanocarriers for the Treatment of Colorectal Cancer 275
https://t.me/med1917
207toxicity (Mitchell et al. 2020). On the other hand, silver NPs are mainly found to kill
208cancer cells by forming reactive oxygen species (ROS) or inducing apoptosis.
209However, silver NPs are known for their toxicity, hence limiting their use in treating
210cancer clinically. This can be overcome by generating more biocompatible silver
211nanoparticles either by constructing core-shell layers or by using it as a drug
212nanocarrier (Sun et al. 2021).
213Meanwhile, silica NPs remain one of the most used inorganic NPs for DDS due to
214their physiochemical properties which are versatile. Mesoporous silica NPs
215(MSNPs) have great biodegradability, high drug-loading capacity and low cytotox-
216icity. Being rich with silanol groups on their surface, MSNPs can interact with
217different functional groups and molecules such as metals, polymers or ligands to
218adjust the properties and functions of the MSNPs (de SL Oliveira et al. 2021).
219Nanotubes, in particular carbon nanotu bes (CNTs), have amassed interest due
220to their multifunctional structure and properties. CNTs are carbon atoms organised
221in a honeycomb nanostructure to form a tubular shape. They are typically
222categorised into two based on carbon atom numbers: multi-wall and single-wall
223CNTs, both having different properties which impact their function as DDS.
224As their unique architecture allows for high surface area for conjugation and/or
225drug loading, and tumour penetration, they are an ideal nanocarrier for targeted
226cancer therapy.
227Quantum dots NPs (QDNPs) are semiconductor nanocrystals made up of heavy
228metal core and outer shell from periodic groups of ii-vi, such as cadmium selenide
229(cdSe) (Devi et al. 2022). They have unique photographic qualities: size-tunable
230light emission, wide absorption coefficient and high excitation of fluorescence
231colours. Though this makes them particularly useful in biomedical applications
232such as bioimaging for drug research and diagnostics, their role as cargo for drug
233delivery remains a challenge due to their poor water solubility and biocompatibility.
234The surface composition of QDNPs, however, can be chemically modified with
235organic biomaterials or inorganic metals to change their physiochemical properties
236and allow them to fit in the biological environment better, commonly known as
237hybrid NPs (Devi et al. 2022).
2382.2.3 Hybrid Nanoparticles
239Polymer-lipid hybrid NPs are an excellent example of hybrid nanocarriers. The drug
240is encapsulated in a hydrophilic/hydrophobic polymeric core and surrounded by a
241lipid layer (Rao and Prestidge 2016). They were developed to overcome the
242shortcomings of both materials, thus enhancing the biodistribution of the drug in
243the system. They inherit polymeric nanocarrier characteristics such as being rich in
244surface chemical modification and profound drug release profile and lipid-based
245nanocarriers’ efficient drug loading capacity and biocompatibility. The improved
246stability and biocompatibility make them an efficient nanocarrier in cancer therapy
247(Rao and Prestidge 2016). Table 1 summarises various types of NPs which show
248promising anticancer action against colorectal cancer.
Соседние файлы в папке Библиотека им академика М.И. Перельмана