Co-delivery of all-trans-retinoic acid and doxorubicin for cancer therapy with synergistic inhibition of cancer stem cells

Nanoparticle-facilitated autophagy inhibition promotes the efficacy of chemotherapeutics against breast cancer stem cells

“…Increasing research has proved that nanoparticle-based platforms could better protect drugs 17 from harsh environments before they can reach the targets, leading to an extended plasma half-life 18 of each drug in the systemic circulation [44]. We also found that use of nanoparticles significantly 19 delayed the clearance of loaded drugs and prolonged circulation half-lives [32]. As expected, the 20 enrichment of CQ, DOX or DTXL in engrafted tumors in mice injected with drug-loaded 21 nanoparticles was significantly higher than that of each free drug administration after 24 h, which 22 may be attributed to the EPR effect and prolonged circulation time.…”

Nanomedicine-mediated cancer stem cell therapy

“…In our recent work, all-trans-retinoic acid (ATRA), a powerful differentiation agent of CSCs, and clinically widely used chemotherapeutic agent DOX are encapsulated together in the same nanoparticle by a single emulsion method to treat breast cancer. We demonstrated that systemic administration of this combinational drug delivery system can markedly augment the enrichment of drugs both in tumour tissues and CSCs in vivo, prodigiously enhance the suppression of tumour growth while reducing the incidence of CSCs in a synergistic manner [47].…”

“…For instance, curcumin-loaded Nano-Curc™ (SignPath Pharmaceuticals, Inc., Pennsylvania, USA; 1.5% curcumin content) was able to significantly suppress anchorage-independent clonogenic growth and reduce the fraction of CD133 þ CSCs in glioblastoma [46]. In our recent work, using a polymer co-delivery system, doxorubicin and all-trans-retinoic acid were delivered to eradicate human breast cancer cells together with CSCs, resulting in enhanced anticancer efficacy compared with free agents [47].…”

Nanoparticulate immunotherapy for cancer

“…ATRA can also act as a powerful cancer stem-cell (CSC) differentiating agent. Sun et al, have shown that simultaneous delivery of ATRA and doxorubicin (DOX) through nanoemulsion, induced breast CSC differentiation, decreased number of breast CSCs in tumor and suppressed tumor growth by attenuating their tumor initiating ability [178]. Wang et al, have investigated the role of pH sensitive nanoparticles in delivery of ATRA.…”