Nanoparticle-based drug delivery in cancer therapy

By Martina Torcè

Innovative drug delivery systems are important in the development of cancer therapy due to the need for precise and contained targeting of the cancerous tissue. The chemotherapeutic agents usually contained in cancer drugs are often delivered non-specifically, which ends up causing high toxicity for the surrounding healthy cells and resulting in low efficiency in treating the cancer cells.1 However, delivering chemotherapeutic agents using nanoparticle-based drug delivery systems mitigates these issues: the drug concentration in cancer cells increases, and the toxicity in normal cells decreases.2

However, the performance of these nanosystems is still limited by several drawbacks due to the complexity of the microenvironment. These include fast body clearance, uncontrollable drug leakage, and low therapeutic index.3 

Particles with a diameter of around 10–1000 nm are considered nanoparticles. The first discovered nanoparticle DDSs were liposomes.4 From then, a multitude of materials have been fabricated into nanoparticles NPs. There are three main categories of NPs. 

Organic NPs, such as liposome-based and polymer-based NPs, were the first kind to be approved for clinical trials. The advantage of this type of NP is that they can mimic the characteristics of the cell membrane, making them very biocompatible. It has been proven that encapsulating chemotherapeutic drugs such as paclitaxel in liposomes have higher anti-tumour efficiency and improved bioavailability compared to free paclitaxel.5

As research on NPs has expanded, inorganic particles have also been investigated for use as NPs in drug delivery, and have several advantages. In contrast to organic NPs, they are less biocompatible, but more stable. They also have a higher loading capacity.6 However, their main advantage is that their surface can be easily modified by conjugation, which gives them a higher surface-area-to-volume ratio. The most widely studied inorganic NPs are gold NPs (AuNPs); the gold core is inert and non-toxic, and they have been shown to increase drug accumulation in tumours.7

Since organic and inorganic NPs each have their own advantages and disadvantages, some research has been done to create a hybrid drug delivery system. An ideal drug nanocarrier should satisfy many criteria, including inherent biocompatibility, high drug-loading dosage, and disease-specific drug accumulation; hybrid nanocarriers are bespoke delivery systems that can address these drug-specific concerns.3 

One type of hybrid NPs is lipid-polymer hybrid NPs, which contain an inner core made of polymers and a lipid shell. This combines the high biocompatibility of lipids with the structural integrity provided by polymer NPs,8 allowing the system to have both hydrophilic and hydrophobic properties.9 This has been shown to be effective in different kinds of cancer including metastatic prostate cancer,10 as it avoids clearance of the system by the reticuloendothelial system.11

Though NPs are a promising method of drug delivery, more research needs to be done to ensure NPs can operate within the complex microenvironment surrounding cancer cells. Further studies on the biological characteristics of individual cancers will inform more specific research directions for these drugs.3

References:

1. Cho K, Wang X, Nie S, Chen Z, Shin DM. Therapeutic Nanoparticles for Drug Delivery in Cancer. Clinical Cancer Research. 2008;14(5):1310-6.

2. Maeda H. The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. Adv Enzyme Regul. 2001;41:189-207.

3. Li M, Luo Z, Zhao Y. Hybrid nanoparticles as drug carriers for controlled chemotherapy of cancer. The Chemical Record. 2016;16(4):1833-51.

4. Gregoriadis G, Ryman BE. Liposomes as carriers of enzymes or drugs: a new approach to the treatment of storage diseases. Biochemical Journal. 1971;124(5):58P-P.

5. Han B, Yang Y, Chen J, Tang H, Sun Y, Zhang Z, et al. Preparation, Characterization, and Pharmacokinetic Study of a Novel Long-Acting Targeted Paclitaxel Liposome with Antitumor Activity. International Journal of Nanomedicine. 2020;Volume 15:553-71.

6. Ghosn Y, Kamareddine MH, Tawk A, Elia C, El Mahmoud A, Terro K, et al. Inorganic nanoparticles as drug delivery systems and their potential role in the treatment of chronic myelogenous leukaemia. Technol Cancer Res Treat. 2019;18:1533033819853241.

7. Yao Y, Zhou Y, Liu L, Xu Y, Chen Q, Wang Y, et al. Nanoparticle-based drug delivery in cancer therapy and its role in overcoming drug resistance. Front Mol Biosci. 2020;7:193.

8. Cheow WS, Hadinoto K. Factors affecting drug encapsulation and stability of lipid-polymer hybrid nanoparticles. Colloids Surf B Biointerfaces. 2011;85(2):214-20.

9. Zhang RX, Ahmed T, Li LY, Li J, Abbasi AZ, Wu XY. Design of nanocarriers for nanoscale drug delivery to enhance cancer treatment using hybrid polymer and lipid building blocks. Nanoscale. 2017;9(4):1334-55.

10. Wang Q, Alshaker H, Böhler T, Srivats S, Chao Y, Cooper C, et al. Core shell lipid-polymer hybrid nanoparticles with combined docetaxel and molecular targeted therapy for the treatment of metastatic prostate cancer. Scientific Reports. 2017;7(1).

11. Hu Y, Hoerle R, Ehrich M, Zhang C. Engineering the lipid layer of lipid–PLGA hybrid nanoparticles for enhanced in vitro cellular uptake and improved stability. Acta Biomaterialia. 2015;28:149-59.

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