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422 N. Nomikou et al.
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You J, et al. Effective photothermal chemotherapy using doxorubicin-loaded gold nanospheres that
target EphB4 receptors in tumors. Cancer Res. 2012;72:4777–86.
You C, et al. Synthesis and biological evaluation of redox/NIR dual stimulus-responsive polymeric
nanoparticles for targeted delivery of cisplatin. Mater Sci Eng C. 2018;92:453–62.
Yuan Q, et al. Photon-manipulated drug release from a mesoporous nanocontainer controlled by
azobenzene-modified nucleic acid. ACS Nano. 2012;6:6337–44.
Yuan Y, et al. Conjugated-polyelectrolyte-based polyprodrug: targeted and image-guided photo-
dynamic and chemotherapy with on-demand drug release upon irradiation with a single light
source. Angew Chem. 2014;126:7291–6.
Yuan Z, et al. Thermosensitive drug-loading system based on copper sulfide nanoparticles for
combined photothermal therapy and chemotherapy in vivo. Biomater Sci. 2018;6:3219–30.
Zangabad PS, et al. Stimulus-responsive liposomes as smart nanoplatforms for drug delivery
applications. Nanotechnol Rev. 2018;7:95–122.
Zhang F, et al. Mesoporous multifunctional upconversion luminescent and magnetic “nanorattle”
materials for targeted chemotherapy. Nano Lett. 2012;12:61–7.
Zhang C, et al. Enzyme-responsive peptide dendrimer-gemcitabine conjugate as a controlled-
release drug delivery vehicle with enhanced antitumor efficacy. Acta Biomater. 2017;55:153–
62.
Zhang C, et al. Rod-based urchin-like hollow microspheres of Bi2S3: facile synthesis, photo-
controlled drug release for photoacoustic imaging and chemo-photothermal therapy of tumor
ablation. Biomaterials. 2020a;237:119835.
Zhang P, et al. Hypoxia-responsive polypeptide nanoparticles loaded with doxorubicin for breast
cancer therapy. ACS Biomater Sci Eng. 2020b;6(4):2167–74.
Zhang P, et al. Charge reversal nano-systems for tumor therapy. J Nanobiotechnol. 2022;20(1):31.
Zhao L, et al. Boronic acid as glucose-sensitive agent regulates drug delivery for diabetes treatment.
Materials (Basel). 2017;10(2):170.
Zhong Q, et al. Polymeric perfluorocarbon nanoemulsions are ultrasound-activated wireless drug
infusion catheters. Biomaterials. 2019;206:73–86.
Zhu C, et al. A eutectic mixture of natural fatty acids can serve as the gating material for near-
infrared-triggered drug release. Adv Mater. 2017;29:1703702.
Zhuo S, et al. pH-sensitive biomaterials for drug delivery. Molecules. 2020;25(23):5649.
Chapter 16
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Nanoparticles and Cancer Chemotherapy
Guojun Xiong and Ijeoma F. Uchegbu
Abbreviations
WHO World Health Organization
mTNBC Metastatic triple-negative breast cancer
NCCN National Comprehensive Cancer Network
EMSO European Society for Medical Oncology
HER2 Human epidermal growth factor receptor 2
PARPi Poly-ADP-ribosyl polymerase inhibitor
US FDA United States Food and Drug Administration
API Active pharmaceutical ingredient
EPR effect Enhanced permeability and retention effect
NIH National Institutes of Health
PET/CT Positron emission tomography/computed tomography
MPS Mononuclear phagocyte system
PEG Polyethylene glycol
DSPE-PCB Distearoyl phosphoethanolamine-polycarboxybetaine
MIRV Mirvetuximab soravtansine
PFS Progression-free survival
ADC Antibody-drug conjugate
TME Tumour microenvironment
APC Antigen-presenting cells
G. Xiong
UCL School of Pharmacy, London, UK
I. F. Uchegbu (*)
UCL School of Pharmacy, University College London, London, UK
e-mail:
ijeoma.uchegbu@ucl.ac.uk
© The Editor(s) (if applicable) and The Author(s), under exclusive license to
Springer Nature Switzerland AG 2024
I. F. Uchegbu et al. (eds.), Fundamentals of Pharmaceutical Nanoscience,
https://doi.org/10.1007/978-3-031-59478-6_16
423
424 G. Xiong and I. F. Uchegbu
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16.1 Introduction
Cancer is a general term for the fatal diseases caused by the abnormal differentiation,
division and uncontrolled growth of the cells, also known as malignant tumours and
neoplasms, and cancer is also the major cause of death globally (Bray et al.
According to the global statistical data (Sung et al. 2021) provided by the World
Health Organization (WHO), approximately 10 million deaths were due to cancer in
2020. Cancers are generally divided into two major categories: malignant tumours
and hematologic cancers. Patients with malignant tumours (excluding blood and
related tumours, such as lymphomas and myelomas) account ed for approximately
90% of the global new cancer cases in 2020 (Sung et al.
2021). From a survey on the
registered causes of cancer deaths in Norway in 2015, an average of 66.7% of the
cancer deaths with different solid tumours were associated with cancer metastasis
(Dillekås et al.
2019). For the deaths caused by ovarian cancer in this survey, the
leading cause in over 90% of deaths was due to metastasis. Cancer metastasis refers
to the spread of cancer cells (which have differentiated from the primary solid
tumour) from primary sites to other organs and tissues through the circulatory system
(Paduch 2016). Therefore, based on the above real-life cancer statistics, metastasis is
the leading cause of death for the most cancer patients. Depending on the development of the tumour, cancer patients can be commonly classified into five stages at the
time of diagnosis (Rosen and Sapra 2023), as listed in Table 16.1. Patients with
Stage 4 cancer are referred to as metastatic cancer patients.
According to the cancer statistics in England (Quaresma et al. 2015), the Nordic
countries (Engholm et al. 2010) and the United States (Siegel et al. 2023), compared
to cancer patients in the twentieth century, with the advancement of diagnostic
techniques and treatment capabilities, the life expectancy of cancer patients in this
century has significantly improved. However, due to the potential for cancer recurrence and metastasis, curing cancer remains challenging. Once malignancies progress to late stages or become unresectable, patients are typically considered
incurable and are provided with palliative treatment (Hui et al.
2018). As a result,
the five-year survival rate of patients with stage 4 cancer is sharply decreased when
compared with that of patients with stage 1, 2 and 3 cancer (Greene and Sobin
In some particular advanced cancers such as metastatic triple-negative breast cancer
(mTNBC), the five-year survival rate for both treated and untreated mTNBC patients
2021).
2008).
Table 16.1 Definition of the stage 0–4 cancer
Stage Definition
0 Carcinoma in situ, the abnormal cells are localized at their original site and has not spread
1 Tumour is small and malignant but has not spread
2 The malignant tumour has grown in its localized area and has not spread
3 The malignant tumour has increased in size and it may spread to the surrounding tissues
and/or lymph nodes
4 The malignant tumour has spread to other sites of the body, which is commonly referred
to as metastatic or advanced cancer
16 Nanoparticles and Cancer Chemotherapy 425
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was less than 10% in one investigation on 608 mTNBC patients diagnosed between
2010 and 2016 (Skinner et al. 2021). The five-year survival rates for patients
diagnosed with stage 4 colorectal cancer in the United States in 2011 and 2017
were 11% and 15%, respectively (Miller et al.
2022). Approximately 20% of patients
with stage 4 colorectal cancer or breast cancer and around 30% of advanced
non-small cell lung cancer patients decided to forgo treatment (Miller et al.
These gruesome death
statistics suggest that there are unmet medical needs for
2022).
effective treatment of some metastatic cancers such as mTNBC and advanced
gastrointestinal cancers (Miller et al.
2022).
In accordance with the clinical practice guidelines (Gennari et al. 2021; National
Comprehensive Cancer Network 2023) from the National Comprehensive Cancer
Network (NCCN) and the European Society for Medical Oncology (ESMO), systemic chemotherapy is recommended as the stand of care or the first-line treatment
for most patients with advanced cancer.
16.2 Cancer Chemotherapy
Chemotherapy is a systemic treatment for cancers and involves the use of alkylating
drugs, antimet abolites, anthracyclines, taxanes and topoisomerase inhibitors for
killing cancer cells systemically (Luo et al.
for different clinical purposes depending on the patient’s cancer. For some cancers,
such as acute leukaemia (Bhatt et al.
2019), systemic chemotherapy is recommended as the primary treatment.
Neoadjuvant chemotherapy (Glynne-Jones et al. 2006) is a treatment used to shrink
the tumour before the surgical resection or radiation therapy. In most instances, the
adjuvant chemotherapy (Rampurwala et al. 2014) is given to cancer patients who
have received the primary treatment or patients with unresectable tumours in order to
inhibit or eliminate the growth of the tumour.
In current treatment strategies, systemic chemotherapy is the mainstay of treatment for most patients with late-stage cancer (Bianchini et al.
2020; Miller et al. 2022). Based on the 2023 National Comprehensive Cancer
Network
®
(NCCN® ) clinical practice guidelines in oncology (NCCN Guidelines® ,
available at https://www.nccn.org/guidelines/category_1), systemic chemotherapybased treatment regimens are recommended as the first-line treatment for most
advanced cancers, such as met astatic non-small cell lung cancer, advanced prostate
cancer, stage 4 cervical cancer, stage 4 bladder cancer and metastatic breast cancer.
As more clinical data has disclosed (Takashima et al.
), combination therapy offers more survival benefits than monotherapy for
2021
cancer patients. Compared to single-agent chemotherapy, some combined chemotherapies have shown synergistic anti-cancer activity in patients. According to the
results of various clinical trials, the median overall survival of metastatic breast
cancer patients who received single-agent chemotherapy with paclitaxel, docetaxel
or a platinum-based drug was approximately 11 to 14 months (Burris
2017). Chemotherapy may be applied
2018) and small cell lung cancer (Sun et al.
2016; Nagayama et al.
2009; Han et al.
2017; Ayoub
1999; Perez
426 G. Xiong and I. F. Uchegbu
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et al. 2001; Isakoff et al. 2015). The clinical data of the phase 3 clinical trial
(NCT02546934) on mTNBC patients (Wang et al. 2022), revealed that the median
overall survival of these mTNBC patients treated with nab-paclitaxel plus cisplatin
and gemcitabine plus cisplatin was 26.3 months and 22.9 months, respectively.
16.3 Other Therapies for Cancer
Surgery, chemotherapy and radiotherapy are the conventional therapies for the
treatment of cancer patients (Tannock 1998). With the technological advances in
immunohistochemistry and cancer genomics (Thennavan et al. 2021), more genes,
proteins and receptors overexpressed in cancer cells have been identified and thus
tumours may be further subdivided based on their molecular characteristics. Based
on these discovered biomarkers, additional systemic therapies are available to
specific cancer patients. The emerging therapies include, but are not limited to,
Poly-ADP-ribosyl polymerase inhibitor (PARPi) therapy, hormone thera py, PI3K/
Akt/mTOR targeted therapy, human epidermal growth factor receptor 2 (HER2)targeted therapy and immunotherapy.
For example, according to different subtypes of breast cancer cells, breast cancer
may be further divided into luminal A-like breast cancer, luminal B-like breast
cancer (HER2-), luminal B-like breast cancer (HER2+), HER2-enriched breast
cancer and triple-negative breast cancer (Harbeck et al.
exploiting these cancer-related biomarkers, patients with luminal A or B breast
cancer may benefit from the hormonal therapy, and patients with HER2-enriched
breast cancer can receive HER2-targeted therapy (Vanneman and Dranoff
addition to the conventional therapies. The progress in tumour genomic profiling has
greatly improved the understanding of inter-tumour heterogeneity and the specific
cell type vulnerabilities have been probed to achieve more targeted treatments
(Arnedos et al.
therapies have failed to demonstrate superiority to conventional chemotherapy in
clinical trials (Janku 2014; Lüönd et al. 2021).
2015; Malone et al. 2020). However, some of these emerging
2019). Therefore, by
2012)in
PARPi Therapy
The mutation of the tumour suppressor or DNA repair genes—BRCA1/2 commonly
occur in various cancer types, including melanoma, ovarian, breast, prostate, lung,
pancreatic and gastrointestinal cancers (Schettini et al.
DNA repair gene—PARP is expected to be overexpressed to encode poly-ADPribosyl polymerase-1/2 to repair the DNA damage caused by the chemotherapeutics
(Chopra et al. 2020). Therefore, a number of PARP inhibitors, such as Olaparib,
Talazoparib, Niraparib, Pazopanib and Rucaparib, have been develo ped for the
clinical treatment of cancer patients with BRCA mutations. Among these, Niraparib
and Rucaparib are recommended by the NCCN® to treat the advanced ovarian
cancer patients who have received at least two lines of chemotherapy. Olaparib
and Talazoparib are recommended by the NCCN and the ESMO for the first-line
2021). Consequently, another
16 Nanoparticles and Cancer Chemotherapy 427
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treatment of mTNBC pati ents with germline BRCA mutations and without the
PD-L1 expression (Gennari et al. 2021).
In theory, combining DNA-damaging agents with PARP inhibitors should
enhance therapeutic efficacy and, consequently, extend the lifespan of patients
with BRCA-mutated cancers. However, in the phase III clinical trial
NCT00938652 (O’Shaughnessy et al.
(PARP inhibitor) in combination with gemcitabine and carboplatin had a similar
median overall survival of 11.1 months versus 11.8 months as mTNBC patients who
received only chemotherapy (gemcitabine + carboplatin). Another phase 3, randomized, double-blind, placebo-controlled clinical tri al, NCT02032277 (Loibl et al.
2018), investigated the impact of adding the PARP inhibitor, veliparib, to the
neoadjuvant chemotherapy in patients with early-stage TNBC and the clinical
outcome of the neoadjuvant chemotherapy (paclitaxel, as a nanoformulation plus
carboplatin) was not statistically significantly different with/without the addition of
the veliparib, with pathological complete response (pCR) values of 53% and 58%,
respectively ( p ¼ 0.36). Lynparza (Olaparib), an FDA-approved PARP inhibitor,
was used as monotherapy for patients with the HER2-negative metastatic breast
cancer (germline BRCA mutation) who had previously received neoadjuvant or
adjuvant chemotherapy in the phase 3 clinical trial, NCT02000622. Patients in the
Olaparib-treated group had significantly improved progression-free survival compared to those in the single-agent chemotherapy arm, 7.0 months versus 4.2 months
(Robson et al.
survival of the patients in the Olaparib-treated group and the single-agent chemotherapy group was not significantly different, 19.3 months versus 17.1 months,
p ¼ 0.531 (Robson et al. 2023). In addition, the talazoparib monotherapy in the
phase 3 EMBRACA trial, NCT01945775, also failed to improve the median overall
survival of patients when compared with the chemotherapy arm, 19.3 months versus
19.5 months (Litton et al.
2017). However, in the follow-up investigation, the median overall
2020).
2014), mTNBC patients who received iniparib
Immunotherapy: Immune Checkpoint Inhibitor
The programmed cell death ligands 1 and 2 (PD-L1, PD-L2) are found in many
cancers (Sciascia et al.
bind with the programmed death receptor 1 (PD-1) of cytotoxic T cells, which allows
the cancer cells to escape attack from the tumour-infiltrating lymphocytes (Dong
et al. 2017). By blocking the interaction between the PD-1 and the PD-L1, the cancer
cells are expected to be decimated by the immune system. Pembrolizumab
(Keytruda) is an immune checkpoint inhibitor (PD-1 inhibitor) and is used as
immunotherapy for advanced non-small cell lung cancer (Pai-Scherf et al.
advanced melanoma (Robert et al.
2017; Suzman et al. 2019) and Hodgkin’s lymphoma (Kuruvilla et al. 2021). PD-L1
expression was found in approximately 20% of TNBC patients (Mittendorf et al.
2014). However, when pembrolizumab was used as monotherapy for patients with
mTNBC in a phase 3 clinical trial, NCT02555657, pembrolizumab monotherapy
failed to improve the overall survival of mTNBC patients in comparison to the use of
capecitabine, eribulin, gemcitabine, or vinorelbine single-agent chemotherapy
2021). The overexpressed programmed cell death ligands
2017),
2015), advanced bladder cancer (Bellmunt et al.
428 G. Xiong and I. F. Uchegbu
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(Winer et al. 2021) and the median overall survival of the mTNBC patients in the
pembrolizumab group and the chemotherapy group was 9.9 months and 10.8 months,
respectively. While in the phase III clinical trial, NCT02819518 (Cortes et al. 2022),
a pembrolizumab plus chemotherapy treatment regimen significantly improved the
median overall survival of mTNBC patients with high expression of PD-L1
(CPS > 10) when compared with the standard chemotherapy group, 23 months
versus 16.1 months.
PI3K/Akt/mTOR Targeted Therapy
The PI3K/Akt signalling pathw ay is a signal transduction pathway within cells that
promotes metabolism, proliferation and cell growth and regulates the cell cycle in
response to extracellular signals (Yang et al.
Akt pathway contributes to tumour growth, angiogenesis and cancer metastasis and
induces drug resistance (He et al.
2019) in this signalling pathway include phosphatidylinositol 3-kinase (PI3K), a
serine/threonine protein kinase (Akt) and mammalian target of rapamycin (mTOR).
In many preclinical studies (Lin et al. 2013; Yan et al. 2014; Cash et al. 2015;
Carnevalli et al. 2018), tumour growth in tumour-bearing mice was significantly
suppressed when the mice were treated with PI3K/Akt/mTOR pathway inhibitors.
However, in a phase 3 clinical trial, NCT02437318, on advanced breast cancer
patients with HR+, HER2- and PIK3CA genetic mutations, the median overall
survival of patients treated with alpelisib (a PI3K inhibitor) and fulvestrant was
not statistically significantly different from that of patients treated with fulvestrant
and placebo: 39.3 months versus 31.4 months respectively (André et al. 2021).
Similarly, in another phase 3 clinical trial, NCT03337724, involving patients with
PIK3CA/AKT1/PTEN-altered HR + HER2- advanced breast cancer, the regimen of
ipatasertib (Akt inhibitor) plus paclitaxel did not provide a greater survival benefit
compared to patients treated with paclitaxel plus placebo, the median progressionfree survival for both arms, as assessed by the investigators was 9.3 months (Turner
et al. 2022). All paclitaxel treatments would have been nanoparticle-based
formulations.
2021). The important nodes (Chamcheu et al.
2019). The aberrantly activated PI3K/
These emerging cancer therapies do provide more treatment options for cancer
patients and many patients have already benefited from advances in cancer treatment. In a study on 40-year trends in survival rates for all cancer patients in England,
the five-year survival rate for all cancers was found to have increased from 29.8% in
1971 to 54.3% in 2011 (Quaresma et al.
survival benefits from these therapies for patients are very limited. Chemotherapy
remains a crucial part of cancer treatment and the combination of both targeted
therapies and chemotherapy may offer the best approach for certain cancer patients
(Conroy et al. 2016
2020; Miller et al. 2022).
2015). However, for advanced cancers, the
; Bianchini et al. 2016; Nagayama et al. 2020; Taieb and Gallois
16 Nanoparticles and Cancer Chemotherapy 429
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16.4 Nanotechnology and Chemotherapeutic Agents
Chemotherapy is a treatment approach that utilizes cytotoxic agents, commonly
referred to as chemotherapeutic agents. These agents are employed to disrupt the
cell growth cycle and ultimately destroy cancer cells. Although chemotherapy is the
most effective and widely used treatment for advanced cancer patients, its serious
side effects, variable efficacy and high treatment costs have led many cancer patients
to consider discontinuing their treatment (Miller et al.
Indeed, many chemotherapeutic drugs exhibit outstanding cytotoxicity against
cancer cells in vitro. For example, Volk-Draper et al. reported IC
paclitaxel in cancer cell lines of MDA-MB-231 and HCC1806 were around 12 nM
(10.25 μg/mL) and 0.78 nM (0.67 μg/mL), respectively (Volk-Draper et al. 2012).
However, the real therapeutic effect of these anti-cancer drugs in cancer patients is
not as great as this in vitro data would suggest. Limitations that affect the performance of anti-cancer drugs in the body include the poor solubility of most active
ingredients (Blume and Schug 1999), various biological barriers (Blanco et al.
2015), non-specific distribution of drugs in organs and tissues, rapid clearance of
drugs from the plasma (Yu et al. 2022) and the complexity of the tumour microenvironment (Swartz et al. 2012). Unfortunately, many drugs with anti-cancer activity
have a low solubility in water, resulting in suboptimal formulations of hydrophobic
drugs or the addition of biologically toxic excipients to solubilize the anti-cancer
drugs. For example, sorafenib (Jiang et al.
2017), an inhibitor of tyrosine protein
kinases, is used for the treatment of hepatocellular carcinoma, advanced renal cell
carcinoma and thyroid cancer. However, sorafenib itself is insoluble in water. The
commercially available sorafenib (Nexavar®) is the tosylate salt of sorafenib.
Although salt formation is a common method to increase the solubility of drugs,
sorafenib tosylate (Nexavar
®
) hardly dissolves in the gastrointestinal tract after oral
administration, resulting in a low and erratic bioavailability of sorafenib in patients
and unnecessary toxicity to patients. Another example is the formulation – Taxol
Taxol® is a conventional chemotherapeutic agent for the systematic treatment of
numerous cancers, including metastatic breast cancer, by parenteral administration
(Gradishar
paclitaxel, biologically toxic excipients, polyethoxylated castor oil and ethanol are
added to the Taxol
2006). Paclitaxel is a hydrophobic anti-cancer drug. In order to solubilize
®
formulation. The lack of an optimal formulation is one of the
major reasons that the promising in vitro performance of these hydrophobic drugs is
difficult to be achieved in vivo.
2022).
values of
50
®
.
Nanoformulations Developed for Oncotherapy
To address the deficiencies of conventional chemotherapeutic drugs in cancer
treatment, the emergence of nanoscale drug delivery systems has ushered in a new
era of systemic chemotherapy. Nanoscale drug delivery systems are a crucial
component of nanomedicines, a term proposed in the 1990s to describe nanoscale
systems or materials designed for various medical purposes (Fornaguera and GarcíaCelma 2017). To date, several nanomedicines have reached the market for the
treatment of cancer (Anselmo and Mitragotri
2019), such as Doxil
®
, Abraxane® ,
430 G. Xiong and I. F. Uchegbu
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Onivyde® and Genexol-PM® , etc. Most nanomedicines have shown improved
pharmacokinetics profiles, reduced systemic toxicity and enhanced therapeutic efficacy, compared to traditional chemotherapeutic drugs with the same active pharmaceutical ingredient (API). For example, doxorubicin hydrochloride is a conventional
formulation of the chemotherapeutic agent (doxorubicin), which is used to treat
various cancers, including breast cancer, blood cancers, bo
cancer and more.
Doxorubicin hydrochlorid e has the serious side effect of
cardiotoxicity. However, when it is encapsulated in liposomes (Doxil
ne sarcoma, ovarian
®
), its
cardiotoxicity is significantly reduced, and its efficacy is significantly improved
(Xing et al.
2015).
The significant advantage of formulating hydrophobic drugs through nanotechnology is that lipophilic drugs can reach high aqueous levels through nanocarriers
without the need for additional toxic excipients in the formulation. For example, the
water solubility of paclitaxel is lower than 50 μg/mL, but when formulated as
albumin-bound paclitaxel nanoparticles (Abraxane
may be increased to at least 2000 μg/mL by these albumin nanocarriers. Furthermore, Abraxane
®
Taxol
contains the organic solvent ethanol and the toxic surfactant, Cremophor
EL. As a result, Abraxane
of paclitaxel, with significantly lower systemic toxicity and greater efficacy for
patients when compared to Taxol
trial (Gradishar et al.
®
is composed of human serum albumin and paclitaxel, while
®
is capable of delivering a higher maximum tolerated dose
®
and this was demonstrated in phase 3 clinical
2005).
®
), aqueous levels of paclitaxel
Approximately 75% of drug candidates (Gala et al. 2020) have poor water
solubility and only 0.02% to 0.04% of prospective anti-cancer drugs are ultimately
approved by the United States Food and Drug Administration (US FDA).
Suboptimal formulation of lipophilic drugs is a significant factor limiting the transition of prospective drugs from the laboratory to clinical applications (Gala et al.
2020). Applying nanotechnology in pharmaceutics allows for the positive improve-
ment of the properties of many conventional drugs (Allen
2004). Various
nanoplatforms, including polymeric nanoparticles, polymer micelles, liposomal
nanoparticles, dendrimers, solid lipid nanoparticles, polymer/antibody-drug conjugates, inorganic nanoparticles and carbon-based nanomaterials, have been developed and applied for diverse medical purposes. These include acting as non-toxic
nanocarriers for peptides, genes, or hydrophobic drugs, and being used as magnetic
resonance imaging contrast agents for tumour imaging and cancer diagnosis. Some
representative FDA-approved nanomedicines are listed in Table
16.2.
16.5 Challenges and Perspectives of Nanomedicines
Indeed, nanomedicines have brought significant advancements to cancer treatment,
but their use also comes with formidable challenges. Nanotechnology has addressed
the issue of suboptimal drug formulations, yet the effective utilization of drugs in the
16 Nanoparticles and Cancer Chemotherapy 431
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Prescription
Marketing
status (2023)
Approval
year Indication(s)
ple myeloma
1996 Magnetic resonance imaging Discontinued
Prescription
Discontinued
metastatic adenocarcinoma of the pancreas
leukaemia
Prescription
amyloidosis
2017 Acute myeloid leukaemia Prescription
https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm
2018 Polyneuropathy of hereditary transthyretin-mediated
Liposome Doxorubicin hydrochloride 1995 Ovarian cancer, AIDS-related Kaposi’ s sarcoma and multi-
®
Product Nanoplatform API
Table 16.2 Representative examples of FDA-approved nanomedicines
Doxil
3
O
2
SPIONs Fe
Liposome Daunorubicin Citrate 1996 Kaposi’s sarcoma Discontinued
®
®
Feridex
DaunoXome
Paclitaxel 2005 Metastatic breast cancer, non-small cell lung cancer and
Liposome Cytarabine 1999 Lymphomatous meningitis Discontinued
Albumin-based
nanoparticle
®
®
DepoCyt
®
Abraxane
Liposome Vincristine sulphate 2012 Philadelphia chromosome-negative acute lymphoblastic
Liposome Irinotecan hydrochloride 2015 Metastatic adenocarcinoma of the pancreas Prescription
Liposome Daunorubicin and
®
®
Marqibo
ONIVYDE
VYXEOS
cytarabine
Transthyretin-directed
small interfering RNA
Lipid
nanoparticle
®
Onpattro
Data source: US FDA Drug Approvals and Databases, available at:
API active pharmaceutical ingredient, AIDS acquired immune deficiency syndrome, FDA food and drug administration, SPION superparamagnetic iron oxide
nanoparticle
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