Nanoparticle-based drug delivery in cancer therapy

Written for Imperial Bioscience Review.

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 (Cho et al., 2008). However, delivering chemotherapeutic agents using nanoparticle-based DDSs, would produce the opposite effect: the drug concentration in cancer cells would increase and the toxicity in normal cells decrease (Maeda, 2001).

However, the performance of these nanosystems is still limited by several drawbacks, such as fast body clearance, uncontrollable drug leakage, and low therapeutic index, due to the complexity of the microenvironment (Li et al., 2016).

Particles with a diameter of around 10–1000 nm are often considered nanoparticles. The first discovered nanoparticle DDSs were liposomes (Gregoriadis et al., 1971). From then, a multitude of materials have been fabricated into NPs. However, there are three main categories. 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 (Han et al., 2020).

As research on NPs has expanded, inorganic particles have also been investigated in their use as NPs for drug delivery, due to having several advantages. In contrast to organic NPs, they are less biocompatible but more stable and have a higher loading capacity (Ghosn et al., 2019). 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 (Yao et al., 2020).

Since organic and inorganic type NPs 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 could switch among different functional components to address specific concerns (Li et al., 2016).

One type of hybrid NPs is lipid-polymer hybrid NPs, which contains 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 (Cheow and Hadinoto, 2011), allowing the system to have both hydrophilic and hydrophobic properties (Zhang R.X. et al., 2017). This has been shown to be effective in different kinds of cancer including metastatic prostate cancer (Wang Q. et al., 2017) as it allows the system to not be cleared by the reticuloendothelial system (Hu et al., 2015).

In conclusion, more research needs to be done to make sure NPs can address the complex microenvironment surrounding cancer cells, but the therapies have already shown promising results.  

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