Physical Properties of Nanoparticles That Result in Improved Cancer Targeting

Abstract

The therapeutic efficacy of drugs is dependent upon the ability of a drug to reach its target, and drug penetration into tumors is limited by abnormal vasculature and high interstitial pressure. Chemotherapy is the most common systemic treatment for cancer but can cause undesirable adverse effects, including toxicity to the bone marrow and gastrointestinal system. Therefore, nanotechnology-based drug delivery systems have been developed to reduce the adverse effects of traditional chemotherapy by enhancing the penetration and selective drug retention in tumor tissues. A thorough knowledge of the physical properties (e.g., size, surface charge, shape, and mechanical strength) and chemical attributes of nanoparticles is crucial to facilitate the application of nanotechnology to biomedical applications. This review provides a summary of how the attributes of nanoparticles can be exploited to improve therapeutic efficacy. An ideal nanoparticle is proposed at the end of this review in order to guide future development of nanoparticles for improved drug targeting in vivo.

Figure 1

Active versus passive tumor targeting. In active targeting, the drug needs a receptor at the tumor surface, whereas in passive targeting, the drug enters the target cells passively.

Figure 2

This figure shows how NPs are coated with proteins once they enter the blood circulation; after a short period of time, proteins came in close contact and form soft corona, and then a final hard protein corona is formed around the NPs containing a fingerprint specific for each individual and tumor.

Figure 3

Effect of varying the NPs size on tissue biodistribution of patient with breast cancer. A 100 nm NPs mostly distribute in the liver, spleen, and kidney, and traces could be found in the breast, whereas, for 20 nm NPs, they mostly distribute in the kidney, spleen, and liver; a moderate amount is able to reach the breast tumor and traces were found in the brain.

Figure 4

Effect of contact angle on the internalization efficacy. Nanoparticles having a prolate ellipsoid morphology (major axis 0.35–2 nm, minor axis 0.2–2 nm) had the slowest internalization rate and the highest attachment rate in comparison to spheroidal morphology (radius 0.26–1.8 nm) and oblate ellipsoidal nanoparticles (major axis 0.35–2.5 nm, minor axis 0.2–2 nm) [37].

Figure 5

Illustration of the time-adaptive BD algorithm: the green circle represents the NPs, the large gray area represents the cells, and P is the probability of NPs to be captured by the NPs (adapted from [81]; open access no permission required).

Figure 6

How different NP shapes could affect the binding avidity of NPs. d is the distance between the receptor and the NP and D is the diameter of the NP.

Figure 7

Proposed ideal NPs characteristics. When NPs are in the blood circulation, it is advantageous to have a larger size (>100 nm) nonspherical shaped NP, with a neutral charge to achieve better circulation and tumor accumulation. Once in contact with the tumor, it is more advantageous to have positively charged or slight negatively charged NPs with a smaller size (<12 nm) and a lower aspect ratio. The surfactants should be removed once the NPs enter the extracellular matrix (ECM).