Efficacy of Surface-Modified PLGA Nanoparticles as a Function of Cervical Cancer Type

Abstract

Purpose-Hypovascularization of cervical tumors coupled with intrinsic and acquired drug resistance, has contributed to marginal therapeutic outcomes by hindering chemotherapeutic transport and efficacy. Recently, the heterogeneous penetration and distribution of cell penetrating peptide (CPP, here MPG) and polyethylene glycol (PEG) modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were evaluated as a function of tumor type and morphology in cervical cancer spheroids modeling hypovascularized tumor nodules. Building upon this work, this study investigates the efficacy imparted by surface-modified Doxorubicin-loaded NPs transported into hypovascularized tissue.Methods-NP efficacy was measured in HeLa, CaSki, and SiHa cells. NP internalization and association, and associated cell viability, were determined in monolayer and spheroid models.Results-MPG and PEG-NP co-treatment was most efficacious in HeLa cells, while PEG NPs were most efficacious in CaSki cells. NP surface-modifications were unable to improve efficacy, relative to unmodified NPs, in SiHa cells. Conclusions-The results highlight the dependence of efficacy on tumor type and the associated microenvironment. The results further relate previous NP transport studies to efficacy, as a function of surface-modification and cell type. Longer-term, this information may help guide the design of NP-mediated strategies to maximize efficacy based on patient-specific cervical tumor origin and characteristics.

Evaluation of the Antitumour and Antiproliferative Effect of Xanthohumol-Loaded PLGA Nanoparticles on Melanoma

“…One of the most used polymers to produce nanoparticles is poly-lactic-co-glycolic acid (PLGA), and it has already been approved for the use in humans by the Food and Drug Administration (FDA) [ 39 ]. PLGA nanoparticles are excellent carriers to encapsulate drugs and deliver them in a sustained, controlled or even targeted manner [ 40 , 41 , 42 , 43 , 44 ]. An increasing interest in the design of polyphenols-loaded PLGA nanoparticles to be applied on tumour imaging [ 45 ] and targeted delivery [ 46 , 47 , 48 , 49 , 50 ] has been noticed in the literature.…”

Acute myocardial infarction therapy using calycosin and tanshinone co-loaded; mitochondrion-targeted tetrapeptide and cyclic arginyl-glycyl-aspartic acid peptide co-modified lipid-polymer hybrid nano-system: preparation, characterization, and anti myocardial infarction activity assessment

“…This phenomenon could be due to the enhanced permeability and retention (EPR) effect in ischemic tissues, which is the primary mechanism of accumulation of passive targeting nanoparticles in the infarct areas (Frangogiannis et al, 2002 ). It was reported that PEG modification could help nanoparticles to escape from phagocytosis and capture by various organs, so that PEGylated nanoparticles had a longer circulation in vivo compared with naked nanoparticles (Sims et al, 2019 ). In vivo pharmacokinetics and tissue distribution in this study showed long-circulating characteristics of NS, which proved that NS system prolonged circulation time of drug and has great potential to accumulate in the myocardial infarct area (He et al, 2011 ).…”

Insulin‑like growth factor axis: A potential nanotherapy target for resistant cervical cancer tumors (Review)

“…The cellular origin of cervical cancer also contributes to the development and diversity of the tumor microenvironment, which creates different obstacles to drug transport, even in tumors of the same size and stage. Additionally, it has been shown that the density of the tumor cells and formation of intercellular junctions serve key roles in the pharmacokinetics of chemotherapeutic agents in solid tumors (13).…”