Comprehensive study of the drug delivery properties of poly( l -lactide)-poly(ethylene glycol) nanoparticles in rats and tumor-bearing mice

Chen

et al. 2019

Adv Funct Materials

Cancer incidence is rising, and the efficacy of current available anticancer agents is limited by severe dose-limiting toxicities and drug resistance problems. Nanoparticles are heralded as the next frontier in cancer treatment. Here, a pure physical method is used to efficiently fabricate very small silver particles even approaching the Ångstrom (Ång) dimension. Fructose is used as a dispersant and stabilizer to coat the Ång-scale silver particles (AgÅPs). Functional and mechanistic studies demonstrate that fructose-coated AgÅPs (F-AgÅPs) can enter and accumulate in multiple cultured cancer cell lines to induce apoptotic death, whereas most normal cells are resistant to the efficacious dose of F-AgÅPs; in vivo, intravenous administration of F-AgÅPs potently inhibits the growth of pancreatic and lung cancer xenografts in nude mice, without inducing notable toxic effects on the healthy tissues. The results suggest the promising potential of F-AgÅPs as a potent, safe, and broad-spectrum agent for the cancer treatment.

Section: Discussionsupporting

confidence: 69%

Ångstrom‐Scale Silver Particles as a Promising Agent for Low‐Toxicity Broad‐Spectrum Potent Anticancer Therapy

Chen

et al. 2019

Adv Funct Materials

“…36-40 Given this, the tumor/liver ratio greater than 1 seen with DiR 3.6 /NPs is unusual. We speculate that the high tumor/liver ratio results from differential dequenching of DiR 3.6 /NPs in liver and tumor ( i.e.…”

Section: Resultsmentioning

confidence: 99%

Quantitative Assessment of Nanoparticle Biodistribution by Fluorescence Imaging, Revisited

et al. 2018

Fluorescence-based whole body imaging is widely used in the evaluation of nanoparticles (NPs) in small animals, often combined with quantitative analysis to indicate their spatiotemporal distribution following systemic administration. An underlying assumption is that the fluorescence label represents NPs and the intensity increases with the amount of NPs and/or the labeling dyes accumulated in the region of interest. We prepare DiR-loaded poly(lactic-co-glycolic acid) (PLGA) NPs with different surface layers (polyethylene glycol with and without folate terminus) and compare the distribution of fluorescence signals in a mouse model of folate-receptor expressing tumor by near infrared fluorescence whole body imaging. Unexpectedly, we observe that fluorescence distribution patterns differ far more dramatically with DiR loading than with the surface ligand, reaching opposite conclusions with the same type of NPs (tumor-specific delivery vs. predominant liver accumulation). Analysis of DiR-loaded PLGA NPs reveal that fluorescence quenching, dequenching and signal saturation, which occur with the increasing dye content and local NP concentration, are responsible for the conflicting interpretations. This study highlights the critical need for validating fluorescence labeling of NPs in the quantitative analysis of whole body imaging. In light of our observation, we make suggestions for future whole body fluorescence imaging in the in vivo evaluation of NP behaviors.

“…The limited RES evasion capacity by PEGylation has been attributed to many phenomena; most importantly, size enlargement of nanocarriers, desorption of PEG from nanocarriers' surfaces and production of anti-PEG antibodies and development of an immune response that causes accelerated blood clearance (ABC) of PEGylated nanocarriers. These are explained in detail as follows; PEGylation causes enlargement of particle size Formulations possessing average particle size ≤ 150-200 nm were reported to be suitable for IV application [7,28,29]; being large enough to avoid filtration in the kidney, and small enough to avoid sequestration in the RES organs (liver, spleen, kidneys), and suitable for selective accumulation and retention in tumor by EPR effect [30][31][32][33][34].…”

Section: Unfavorable Physicochemical Properties Of Pegylated Nanocarrmentioning

confidence: 99%

Limitations of Pegylated Nanocarriers: Unfavourable Physicochemical Properties, Biodistribution Patterns and Cellular and Subcellular Fates

Sebak

2018

Int J App Pharm

Assuming that polyethylene glycol (PEG)-conjugated or PEGylated nanocarriers always offer outstanding physicochemical properties and pharmacokinetics profiles when compared to non-PEGylated ones, is not always accurate. For example, drug-loaded PEGylated nanocarriers for the treatment of cancer will not magically escape the reticuloendothelial system (RES) sequestration and clearance, benefit from the enhanced permeability and retention (EPR) effect of the tumor leaky vasculature and preferentially accumulate in the target tissue or cells. This is too good to be true. In this review, several drawbacks of PEGylation will be discussed; for example, how PEGylation can give rise to unfavourable physicochemical characteristics (e. g. particle size and release patterns) and post in vivo administration limitations of the formulated nanocarriers (e. g. limited evasion of RES uptake, development of hypersensitivity reactions, reduced intracellular accumulation and interference with the subcellular processing of nanocarriers necessary to produce the intended pharmacological effect).This review aims at providing better understanding of the pros and cons of PEGylation, encouraging the use of PEGylation with caution, avoiding the assumption that PEGylation will provide all advantages needed to deliver nanocarriers to the target tissue and looking for alternatives to optimize nanocarriers’ utilization especially in the delivery of chemotherapeutic agents for the treatment of different types of cancer. This review comprises a summary of some of the reported literature between 2013 and 2018 using different search engines; PubMed, Science Direct and Google Scholar, and the keywords listed below.