PEGylated-PLGA Nanoparticles Coated with pH-Responsive Tannic Acid-Fe(III) Complexes for Reduced Premature Doxorubicin Release and Enhanced Targeting in Breast Cancer.

Biodegradable poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) have been widely used as delivery vehicles for chemotherapy drugs. However, premature drug release in PLGA NPs can damage healthy tissue and cause serious adverse effects during systemic administration. Here, we report a tannic acid-Fe(III) (FeIII-TA) complex-modified PLGA nanoparticle platform (DOX-TPLGA NPs) for the tumor-targeted delivery of doxorubicin (DOX). A PEGylated-PLGA inner core and FeIII-TA complex outer shell were simultaneously introduced to reduce premature drug release in blood circulation and increase pH-triggered drug release in tumor tissue. Compared to the unmodified NPs, the initial burst rate of DOX-TPLGA NPs was significantly reduced by nearly 2-fold at pH 7.4. Moreover, the cumulative drug release rate at pH 5.0 was 40% greater than that at pH 7.4 due to the pH-response of the FeIII-TA complex. Cellular studies revealed that the TPLGA NPs had enhanced drug uptake and superior cytotoxicity of breast cancer cells in comparison to free DOX. Additionally, the DOX-TPLGA NPs efficiently accumulated in the tumor site of 4T1-bearing nude mice due to the enhanced permeability and retention (EPR) effect and reached a tumor inhibition rate of 85.53 ± 8.77% (1.31-fold versus DOX-PLGA NPs and 3.12-fold versus free DOX). Consequently, the novel TPLGA NPs represent a promising delivery platform to enhance the safety and efficacy of chemotherapy drugs.

A novel liposome-polymer hybrid nanoparticles delivering a multi-epitope self-replication DNA vaccine and its preliminary immune evaluation in experimental animals.

DNA vaccine is an attractive immune platform for the prevention and treatment of infectious diseases, but existing disadvantages limit its use in preclinical and clinical assays, such as weak immunogenicity and short half-life. Here, we reported a novel liposome-polymer hybrid nanoparticles (pSFV-MEG/LNPs) consisting of a biodegradable core (mPEG-PLGA) and a hydrophilic shell (lecithin/PEG-DSPE-Mal 2000) for delivering a multi-epitope self-replication DNA vaccine (pSFV-MEG). The pSFV-MEG/LNPs with optimal particle size (161.61 ±â€¯15.63 nm) and high encapsulation efficiency (87.60 ±â€¯8.73%) induced a strong humoral (3.22-fold) and cellular immune responses (1.60-fold) compared to PBS. Besides, the humoral and cellular immune responses of pSFV-MEG/LNPs were 1.58- and 1.05-fold than that of pSFV-MEG. All results confirmed that LNPs was a very promising tool to enhance the humoral and cellular immune responses of pSFV-MEG. In addition, the rational design and delivery platform can be used for the development of DNA vaccines for other infectious diseases.

Multiple targeting strategies achieve novel protein drug delivery into proapoptosis lung cancer cells by precisely inhibiting survivin.

Therapeutic recombinant proteins have numerous advantages and benefits over chemical drugs, particularly high specificity and good biocompatibility. However, the therapeutic potential and clinical application of current anticancer protein drugs are limited as most biomarkers are located within cells, and multiple physiological barriers exist between the point of administration and the intracellular biomarker. Herein, we report a novel strategy to accurately deliver a cell-permeable dominant-negative TATm-Survivin (TmSm) protein (T34A) to intracellular survivin in cancer cells by overcoming multiple barriers in vivo. A poly(d,l-lactide-co-glycolide) (PLGA) inner core, a polyethylene glycol (PEG) modification, and a TATm peptide were simultaneously introduced to mediate tumor tissue targeting and response to pH-triggered TmSm release. Compared to free TmSm, the PEGylated-PLGA nanoparticle platform achieved a significantly higher cellular uptake efficiency (1.79-fold for A549 and 1.77-fold for Capan-2), effectively decreased IC50 (1.22-fold for A549 and 1.17-fold for Capan-2), and largely elevated apoptosis in different cancer cells (1.17-fold for A549 and 1.15-fold for Capan-2). Besides, this newly developed nanoplatform showed increased protein drug accumulation in the tumor site in A549-bearing nude mice and reached a tumor inhibition rate of 55.81% (1.35-fold versus free TmSm) by reducing the expression of intracellular survivin. All these results confirmed that our newly developed delivery strategy is a very promising tool, which helps protein drugs to cross multiple barriers in vivo and achieves precise targeting to intracellular biomarkers. This strategy could also be applied to other types of protein drugs to further improve their clinical anticancer therapeutic efficacy.