Functionalization of Nanoparticulate Drug Delivery Systems and Its Influence in Cancer Therapy

Abstract

Research into the application of nanocarriers in the delivery of cancer-fighting drugs has been a promising research area for decades. On the other hand, their cytotoxic effects on cells, low uptake efficiency, and therapeutic resistance have limited their therapeutic use. However, the urgency of pressing healthcare needs has resulted in the functionalization of nanoparticles' (NPs) physicochemical properties to improve clinical outcomes of new, old, and repurposed drugs. This article reviews recent research on methods for targeting functionalized nanoparticles to the tumor microenvironment (TME). Additionally, the use of relevant engineering techniques for surface functionalization of nanocarriers (liposomes, dendrimers, and mesoporous silica) and their critical roles in overcoming the current limitations in cancer therapy-targeting ligands used for targeted delivery, stimuli strategies, and multifunctional nanoparticles-were all reviewed. The limitations and future perspectives of functionalized nanoparticles were also finally discussed. Using relevant keywords, published scientific literature from all credible sources was retrieved. A quick search of the literature yielded almost 400 publications. The subject matter of this review was addressed adequately using an inclusion/exclusion criterion. The content of this review provides a reasonable basis for further studies to fully exploit the potential of these nanoparticles in cancer therapy.

Keywords: cancer therapy; dendrimers; liposomes; mesoporous silica NPs; multifunctional nanoparticles (MNPs); surface functionalization.

Figure 1

Graphical representation of the abstract. Illustration of tumor microenvironment and how surface-functionalized nanocarriers containing antitumor drugs actively target tumor cells.

Figure 2

Nanoparticles’ classifications, applications, and differences.

Figure 3

Targeted liposomes having two peptides (TfR- and VEGFR2-specified peptides) and two antitumor agents (doxorubicin and vincristine). (a) Cellular uptake (After 2 h at 37 °C, cellular uptake of Cy5.5-loaded liposomes of varying densities of T7 (A) and DA7R (B) in C6 cells. The cells’ auto-fluorescence was used as the control. Cellular uptake of varied Cy5.5 loaded lyposomes by bEND.3 cells (C), HUVECs (D), and C6 (E) cells); (b) cytotoxicity study (The cytotoxic activity of free DOX + free VCR, as well as some liposomes containing DOX and VCR); (c) biodistribution study (The biodistribution of Cy5.5 in varied liposomes in mice with intracranial C6 glioma was ascertained using an IVIS® Spectrum-CT (A). A CLSM was used to show the allocation of Cy5.5 in the brains of mice with intracranial C6 glioma (B). 16 days after inoculation, MRI of physiologic and pathological brains (C). Glioma tumor cell division rate in the brain (D). Survival curves according to Kaplan–Meier (E). The yellow line represents the intracranial glioma margin, and the arrow represents the glioma cells. The red is Cy5.5, and the nuclei are stained with DAPI (blue). Effectiveness after treatment with different formulations at 1 mg/kg (DOX 0.8 mg/kg + VCR 0.2 mg/kg) on days 8, 10, 12, and 14 after inoculation.) This designed system could go through the blood–brain barrier and blood–tumor barrier, with enhanced cellular uptake and cytotoxicity [32]. Copyright 2017, Taylor & Francis Journals. * p < 0.05.

Figure 4

Illustration of the types of functionalization on the nanoparticulate drug delivery systems.