Co-delivery of doxorubicin and siRNA by all-trans retinoic acid conjugated chitosan-based nanocarriers for multiple synergistic antitumor efficacy.

To achieve the co-delivery of doxorubicin (DOX) and small interfering RNA (siRNA) targeting B-cell lymphoma 2 (siBcl-2), lactose acid (LA) and all-trans retinoic acid (ATRA) double grafted N,N,N-trimethyl chitosan (TMC) nanoparticles (GTA NPs) were developed. The relative viability of QGY-7703 cells was decreased to 81.3% when the concentration of GTA NPs was 0.1 mg/mL, but no toxicity to normal cells was observed, indicating that the GTA NPs selectively inhibited the proliferation of tumor cells. With DOX loaded into the hydrophobic core and siRNA condensed onto the hydrophilic shell, GTA/DOX/siRNA NPs were prepared. The GTA/DOX/siRNA NPs possessed high cellular uptake via receptor-mediated endocytosis. Owing to multiple cooperative antitumor effects of DOX, siBcl-2, and GTA NPs, GTA/DOX/siRNA NPs had superior in vitro and in vivo antitumor efficiency to other formulations. These findings provide a guideline for the combined applications of multiple synergistic antitumor manners.

Liu C ，Tang C ，Yin C 《-》

Enhanced antitumor efficacy of arginine modified amphiphilic nanoparticles co-delivering doxorubicin and iSur-pDNA via the multiple synergistic effect.

Arginine and α-tocopherol succinate (α-TOS) double grafted N-trimethyl chitosan chloride (TMC) nanoparticles (TAS NPs) were designed and developed for effective co-delivery of doxorubicin (DOX) and Survivin shRNA-expressing pDNA (iSur-pDNA). With DOX loading into the hydrophobic core and iSur-pDNA combining to the hydrophilic shell, TAS/DOX/pDNA NPs demonstrated favorable structural stability and sustained release properties in vitro. With the special non-clathrin-dependent endocytosis, TAS/DOX/pDNA NPs presented higher cellular uptake and mainly distributed in ER and Golgi rather than lysosomes following internalization. The in vitro nuclear localization, gene silencing efficiency, cell apoptosis, and growth inhibition of tumor cells were significantly promoted by arginine modification. In the tumor-bearing mice model, TAS/DOX/pDNA NPs possessed the maximum antitumor efficiency as compared with single delivery of DOX or iSur-pDNA. Particularly, blank TAS NPs were selectively be toxic to tumor cells as evidenced by their capabilities to inhibit proliferation and induce apoptosis of tumor cells. The promising tumor treatment of TAS/DOX/pDNA NPs via a multiple synergistic manner arising from DOX and pDNA as well as the vectors would provide a potential strategy for a dual-delivery system to improve their therapeutic efficacies.

Song Y ，Tang C ，Yin C 《-》

Host-guest supramolecular hydrogel based on nanoparticles: co-delivery of DOX and siBcl-2 for synergistic cancer therapy.

Peng D ，Gao H ，Huang P ，Shi X ，Zhou J ，Zhang J ，Dong A ，Tang H ，Wang W ，Deng L ... -  《-》

Co-delivery of doxorubicin and interleukin-2 via chitosan based nanoparticles for enhanced antitumor efficacy.

In order to reduce toxicity and improve antitumor therapeutic effects of doxorubicin (DOX) and recombinant human interleukin-2 (rhIL-2), we developed a hydrophilic cationic polymer (N,N,N-trimethyl chitosan, TMC) based nanocomplexes (FTCD/rhIL-2) which could efficiently mediate systemic co-delivery of hydrophobic DOX and water-soluble rhIL-2 to achieve the purpose of combination therapy. DOX was covalently conjugated to TMC through cis-aconitic anhydride (CA) which endowed nanocomplexes a pH-sensitive release of DOX, while rhIL-2 was loaded through electrostatic adsorption without compromise of bioactivity. The resultant nanocomplexes exhibited sub-spherical shape (∼200nm) and positive charge (>20mV). Folate (FA) modification was utilized with the intention of active targeting, which was however correlated with weakened tumor growth inhibition, emphasizing the importance of balance in overcoming diverse delivery barriers for efficacious antitumor therapy. Compared with free drugs, FTCD/rhIL-2 nanocomplexes significantly delayed tumor growth, increased the serum immunoglobulin G (IgG) level and the amount of tumor infiltrated cytotoxic T lymphocytes. These results indicated that the combinational administration of DOX and rhIL-2 based on polymer nanoparticles could serve as an effective strategy in antitumor therapy. Combined administration of doxorubicin (DOX) and recombinant human interleukin-2 (rhIL-2) has been utilized for the treatment of tumors. However the traditional administration brought to severe side effects, and the efficiency of current delivery systems were unsatisfactory. Herein we developed a hydrophilic cationic polymer based nanoparticle delivery system which facilitated simultaneous and systemic co-delivery of hydrophobic DOX and water-soluble rhIL-2. This system achieved pH-sensitive release of DOX and sustained release of rhIL-2 in vitro, meanwhile, improved anti-tumor efficacy and reduced side-effect in vivo. Thus, our study provided a solution for combinational administration of DOX and rhIL-2 and could serve as an effective strategy in antitumor therapy.

Wu J ，Tang C ，Yin C 《-》

D-α-tocopherol polyethylene glycol 1000 succinate-modified liposomes with an siRNA corona confer enhanced cellular uptake and targeted delivery of doxorubicin via tumor priming.

Tan X ，Fang Y ，Ren Y ，Li Y ，Wu P ，Yang X ，Liu W ... -  《-》