Docetaxel (DTX)-loaded polymeric micelles (DTBM) were formulated using the triblock copolymer, poly(ethylene glycol)–polylactide–poly(ethylene glycol) (PEG–PLA–PEG), to comprehensively study their pharmaceutical application as anticancer nanomedicine. DTBM showed a stable formulation of anticancer nanomedicine that could be reconstituted after lyophilization (DTBM-R) in the presence of PEG 2000 and D-mannitol (Man) as surfactant and protectant, respectively. DTBM-R showed a particle size less than 150 nm and greater than 90% of DTX recovery after reconstitution. The robustly formed micelles might minimize systemic toxicity due to their sustained drug release and also maximize antitumor efficacy through increased accumulation and release of DTX from the micelles. From the pharmaceutical development point of view, DTBM-R showing successful reconstitution could be considered as a potent nanomedicine for tumor treatment.

Currently, one of the most important challenges in the development of nanotechnology-based anticancer treatments is the failure of nanoparticles to escape from the endo-lysosomal compartment and the resulting elimination of endocytosed nanoparticles via the exocytosis pathway without drug release. A pH-sensitive nanoparticle composed of poly(ethylene glycol)–poly(L-lysine)(-grafted 2,3 dimethyl maleic anhydride)–poly(lactic acid) triblock copolymer (PEG–PLL(-g-DMA)–PLA) with a pro-apoptotic peptide (D-(KLAKLAK)₂) and an anticancer drug doxorubicin (Dox) (DTM(Pep, Dox)) was prepared and evaluated for its antiproliferative activity against tumor cells. Due to the membrane-lytic ability of the peptide and the “proton sponge” effect of the pH-sensitive nanocarrier, DTM(Pep, Dox) accelerated the disruption of the endo-lysosomal membrane and displayed enhanced anticancer activities, arising from strong synergism, under in vitro and in vivo conditions. The prepared formulations are anticipated to be of potential use in nanotechnology-based combination therapy and it is believed that this novel formulation will have new applications in advanced tumor therapy.

Poly(aspartic acid-graft-imidazole)-poly(ethylene glycol) (P(Asp-g-Im)-PEG) was utilized as a pH-sensitive nanocarrier of the photosensitizer indole-3-acetic acid (IAA) for the treatment of skin cancer. IAA loaded micelles (ILMs) exhibited the formation of ca. 140 nm spherical particles at pH 7.4. The micelles disintegrated at acidic pHs, resulting in pH-dependent IAA release and cytotoxicity. Treatment of ILMs with visible light at a wavelength of 480 nm caused pH dependent synergistic cell damage in both in vitro and in vivo models using the B16F10 melanoma cell line. Interestingly, ILMs synergistically produced reactive oxygen species (ROS) at an acidic pH of 6.5 with visible light irradiation by proton coupled electron transfer (PCET). The pH sensitive ILMs could be considered a potent nanomedicine used to exert synergistic photodynamic therapeutic effects to treat cancers.

Combination therapy is considered to be a promising strategy for improving the therapeutic efficiency of cancer treatment. In this study, an on-demand pH-sensitive nanocluster (NC) system was prepared by the encapsulation of gold nanorods (AuNR) and doxorubicin (DOX) by a pH-sensitive polymer, poly(aspartic acid-graft-imidazole)-PEG, to enhance the therapeutic effect of chemotherapy and photothermal therapy. At pH 6.5, the NC systems formed aggregated structures and released higher drug amounts while sustaining a stable nano-assembly, structured with less systemic toxicity at pH 7.4. The NC could also increase antitumor efficacy as a result of improved accumulation and release of DOX from the NC system at pH_ex and pH_en with locally applied near-infrared light. Therefore, an NC system would be a potent strategy for on-demand combination treatment to target tumors with less systemic toxicity and an improved therapeutic effect.