Enhanced in vitro and in vivo therapeutic efficacy of codrug-loaded nanoparticles against liver cancer

Abstract

Paclitaxel (Ptx), one of the most widely used anticancer agents, has demonstrated extraordinary activities against a variety of solid tumors. However, the therapeutic response of Ptx is often associated with severe side effects caused by its nonspecific cytotoxic effects and special solvents (Cremophor EL ® ). The current study reports the stable controlled release of Ptx/tetrandrine (Tet)-coloaded nanoparticles by amphilic methoxy poly(ethylene glycol)-poly(caprolactone) block copolymers. There were three significant findings. Firstly, Tet could effectively stabilize Ptxloaded nanoparticles with the coencapsulation of Tet and Ptx. The influence of different Ptx/Tet feeding ratios on the size and loading efficiency of the nanoparticles was also explored. Secondly, the encapsulation of Tet and Ptx into nanoparticles retains the synergistic anticancer efficiency of Tet and Ptx against mice hepatoma H22 cells. Thirdly, in the in vivo evaluation, intratumoral administration was adopted to increase the site-specific delivery. Ptx/Tet nanoparticles, when delivered intratumorally, exhibited significantly improved antitumor efficacy; moreover, they substantially increased the overall survival in an established H22-transplanted mice model. Further investigation into the anticancer mechanisms of this nanodelivery system is under active consideration as a part of this ongoing research. The results suggest that Ptx/Tet-coloaded nanoparticles could be a potential useful chemotherapeutic formulation for liver cancer therapy.

Lactoferrin-modified PEGylated liposomes loaded with doxorubicin for targeting delivery to hepatocellular carcinoma

“…25 Changes in body weight of each mouse were monitored during the treatment to evaluate possible toxic effects of the therapy.…”

“…Then the postmortem tumor was harvested, washed, photographed, and weighted. 25 The tumor weight inhibition (TWI) was calculated from the formula…”

An efficient Trojan delivery of tetrandrine by poly(N-vinylpyrrolidone)-block-poly(ε-caprolactone) (PVP-b-PCL) nanoparticles shows enhanced apoptotic induction of lung cancer cells and inhibition of its migration and invasion

“…23 In our previous studies, Tet-loaded mPEG-PCL nanoparticles showed an antitumor effect in several gastrointestinal cancer cell lines. [24][25][26] We demonstrated that Tet-loaded mPEG-PCL nanoparticles showed enhanced antitumor efficiency compared to free Tet through more efficient penetration of cell membrane by endocytosis. 25 Recently the application of nanoparticle systems in tumor imaging and therapy has attracted more and more interest.…”

“…As demonstrated in our previous studies, cellular uptake of nanoparticles is mediated by endocytosis, which penetrates cell membranes more efficiently than the infiltration of small molecules. [24][25][26]48,49 Therefore, cellular uptake of TetNPs mediated by endocytosis leads to more intracellular Tet accumulation, thereby more effectively regulating the …”

Tetrandrine, a Chinese plant-derived alkaloid, is a potential candidate for cancer chemotherapy

“…When delivered intratumorally, Ptx/Tet nanoparticles exhibited significantly improved antitumor efficacy in the in vivo evaluation as intratumoral administration was adopted to increase site-specific delivery. Moreover, the combination substantially increased the overall survival in an established H22-transplanted mouse model [117]. Thus, Ptx/Tet-coloaded nanoparticles could be a potentially useful chemotherapeutic formulation for liver cancer therapy.…”