At present, combined therapy has become an effective strategy for the treatment of cancer. Co-delivery of the chemotherapeutic drugs and siRNA can more effectively inhibit tumor growth by nano drug delivery systems (NDDSs). Here, we prepared and evaluated a multifunctional envelope-type nano device (MEND). This MEND was a kind of composite lipid-nanoparticles possessing both the properties of liposomes and nanoparticles. In this study, an acid-cleavable ketal containing poly (β-amino ester) (KPAE) was used to bind siBCL-2 and the KPAE/siBCL-2 complexes were further coated by epirubicin (EPI) containing lipid to form EPI/siBCL-2 dual loaded lipid-nanoparticles. The results showed that the average size of EPI/siBCL-2-MEND was about 120 nm, and the average zeta potential was about 41 mV. The encapsulation efficiency (EE) of EPI and siBCL-2 was 86.13% and 97.07%, respectively. EPI/siBCL-2 dual loaded lipid-nanoparticles showed enhanced inhibition efficiency than individual EPI-loaded liposomes on HepG cells by MTT assay. Moreover, western blot experiment indicated co-delivery of EPI/siBCL-2 can significantly down-regulate the expression of P-glycoprotein (P-gp), while free EPI and EPI-loaded liposomes up-regulated it. Therefore, the strategy of co-delivering EPI and siBCL-2 simultaneously by lipid-nanoparticles showed promising potential in reversing multidrug resistance of tumor cells.

Poor tumour penetration became a major challenge for the use of nanoparticles in anticancer therapy. To further enhance the tumour penetration efficiency, we developed a tumour-microenvironment-responsive multistage drug delivery system which was formed layer by layer via electrostatic interaction with cationic drug-loaded nanoparticles, hyaluronidase (HAase) and iRGD-modified gelatin (G-iRGD). The drug-loaded nanoparticles were formed by self-assembling mPEG-PDPA-PG and encapsulation with epirubicin (EPI). Due to the protonation of tertiary amine groups of PDPA segment in acid environment, mPEG-PDPA-PG could enhance the lysosomal escape and the intracellular release of EPI. This NPs/HAase/G-iRGD delivery system showed great biocompatibility in vitro, confirmed by MTT method. In vitro spherical tumour model penetration and in vivo tumour permeability investigation showed HAase coated NPs-EPI (NPs-EPI/HAase) could significantly enhance its penetrating efficiency. The NPs-EPI/HAase could assist in breaking down the hyaluronic acid (HA), which was a key component of extracellular matrix and thereby improving mass transport within the solid tumours. The flow cytometry studies showed that G-iRGD coated NPs-EPI (NPs-EPI/G-iRGD) was more easily taken up by HepG2 cells than gelatin coated NPs-EPI (NPs-EPI/G), which revealed the active targeting ability of iRGD. The results proved that this NPs/HAase/G-iRGD delivery system showed promising potential in enhancing tumour penetration efficiency.

With the merits of excellent efficacy, safety, and facile implementation, antibacterial photodynamic therapy (APDT) represents a promising means for treating bacterial infections. However, APDT shows an unsatisfactory efficacy in combating antibiotic-resistant Gram-negative bacteria due to their specific cell wall structure. In this work, we report a perfluorocarbon nanoemulsion (Ce6@FDC) used as a multifunctional nanocargo of photosensitizer and oxygen for sensitizing antibiotic-resistant Gram-negative bacteria to APDT. Ce6@FDC was fabricated via ultrasonic emulsification with good colloidal stability, efficient Ce6 and oxygen delivery, and excellent photodynamic activity. Meanwhile, Ce6@FDC could strongly bind with Gram-negative Acinetobacter baumannii (A. baumannii) and Escherichia coli (E. coli) via electrostatic interaction, thus leading to notable photodynamic bactericidal potency upon irradiation. In addition, oxygenated Ce6@FDC also exhibited a remarkable efficacy in eradicating Gram-negative bacteria biofilm, averaging five log units lower than the Ce6 group under identical conditions. Taken together, we demonstrate that photodynamic perfluorocarbon nanoemulsion with oxygen-delivery ability could effectively kill planktonic bacteria and remove biofilm, representing a novel strategy in fighting against antibiotic-resistant Gram-negative bacteria.

The aim of this study was to prepare small-molecule camptothecin (CPT) prodrugs and evaluate their effectiveness in colorectal carcinoma therapy. Prodrug nanoparticles (NPs) were physicochemically characterized and evaluated for their cytotoxicity in human colon cancer (HCT116) cell lines. The antitumor efficacy of the NPs was evaluated in HCT116 tumor-bearing mice. The prepared NPs exhibited high drug loading capacity (32% of CPT w/w) and also kept a high active lactone fraction of CPT (>85%) during circulation. The NPs were internalized into tumor cells efficiently compared with free drug and significantly enhanced the drug's therapeutic efficacy. The developed small-molecule CPT prodrug NPs could be a promising strategy in the clinical therapy of colorectal carcinoma.

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