Molecular targeting of liposomal nanoparticles to tumor microenvironment

Abstract

Liposomes are biodegradable and can be used to deliver drugs at a much higher concentration in tumor tissues than in normal tissues. Both passive and active drug delivery by liposomal nanoparticles can significantly reduce the toxic side effects of anticancer drugs and enhance the therapeutic efficacy of the drugs delivered. Active liposomal targeting to tumors is achieved by recognizing specific tumor receptors through tumor-specific ligands or antibodies coupled onto the surface of the liposomes, or by stimulus-sensitive drug carriers such as acid-triggered release or enzyme-triggered drug release. Tumors are often composed of tumor cells and nontumor cells, which include endothelial cells, pericytes, fibroblasts, stromal, mesenchymal cells, innate, and adaptive immune cells. These nontumor cells thus form the tumor microenvironment, which could be targeted and modified so that it is unfavorable for tumor cells to grow. In this review, we briefly summarized articles that had taken advantage of liposomal nanoparticles as a carrier to deliver anticancer drugs to the tumor microenvironment, and how they overcame obstacles such as nonspecific uptake, interaction with components in blood, and toxicity. Special attention is devoted to the liposomal targeting of anticancer drugs to the endothelium of tumor neovasculature, tumor associated macrophages, fibroblasts, and pericytes within the tumor microenvironment.

Effects of Tumor Microenvironment Heterogeneity on Nanoparticle Disposition and Efficacy in Breast Cancer Tumor Models

“…Based on the evidence, we evaluated TAMs in association with tumor delivery and efficacy of PLD compared to NL-doxo in two breast tumor subtypes. The baseline level of TAMs were similar between two models, which indicates that the level of TAMs may not account for the variable tumor delivery of PLD in these breast tumor subtypes (38, 39). However, the different changes of TAMs over time after NL-doxo or PLD in two models implicate the drug- and tumor-dependent interaction between TAMs and drugs.…”

GPR4 decreases B16F10 melanoma cell spreading and regulates focal adhesion dynamics through the G13/Rho signaling pathway

“…There may be an avenue for chemical therapy and gene-based therapy by targeting the pH-sensing GPCRs such as GPR4. In search for approaches to minimize therapy-related side effects, acid-released nanoparticles have been investigated to specifically deliver drugs, siRNAs, and gene constructs to the acidic microenvironment [22,78]. One such method uses polyethylene glycol (PEG)-based hydrogels integrated with imidazole to release therapeutics (Antagomir) in acidic environments [22].…”

Lipobeads

“…In particular, three ways to facilitate the intracellular drug delivery include (i) introduction of fusogenic lipids or membrane active peptides into liposomal bilayer enhances fusion or even disruption of cell/organelle membrane and thereby improves cytoplasmic delivery of drug [81][82][83][84][85], (ii) utilization of macrophages for natural endocytosis of drug-loaded liposomes [86], and (iii) receptor-mediated endocytosis of ligand-targeted liposomal drug carriers into the intracellular compartment (see reviews [87][88][89][90]). …”

“…Strategies of active cell targeting which has been proposed for liposomal carriers [86][87][88] could be applicable to lipobeads as well.…”