Hypoxia-Responsive Polymersomes for Drug Delivery to Hypoxic Pancreatic Cancer Cells

Abstract

Hypoxia in tumors contributes to overall tumor progression by assisting in epithelial-to-mesenchymal transition, angiogenesis, and metastasis of cancer. In this study, we have synthesized a hypoxia-responsive, diblock copolymer poly(lactic acid)–azobenzene–poly(ethylene glycol), which self-assembles to form polymersomes in an aqueous medium. The polymersomes did not release any encapsulated contents for 50 min under normoxic conditions. However, under hypoxia, 90% of the encapsulated dye was released in 50 min. The polymersomes encapsulated the combination of anticancer drugs gemcitabine and erlotinib with entrapment efficiency of 40% and 28%, respectively. We used three-dimensional spheroid cultures of pancreatic cancer cells BxPC-3 to demonstrate hypoxia-mediated release of the drugs from the polymersomes. The vesicles were nontoxic. However, a significant decrease in cell viability was observed in hypoxic spheroidal cultures of BxPC-3 cells in the presence of drug encapsulated polymersomes. These polymersomes have potential for future applications in imaging and treatment of hypoxic tumors.

Reduction and pH dual‐responsive block copolymers containing pendent p‐nitrobenzyl carbamate functionalities: Synthesis and self‐assembly behavior

“…[27][28][29] As the azobenzene units were reduced to the corresponding anilines by azoreductase under the hypoxic condition, the polymeric assemblies formed by azobenzene-containing polymers successfully released the encapsulated drugs or siRNA to hypoxic cancer cells. 30,31 It was found that doxorubicin (DOX)-loaded nanoparticles of nitroimidazolemodified polymers selectively accumulated at the hypoxic tumor tissues and exhibited high antitumor activity in vivo. 32 Under hypoxic conditions, p-nitrobenzyl alcohol derivatives (NADs) are highly labile and readily degraded by a 1,6-elimination reaction in the presence of NTR with nicotinamide adenine dinucleotide as an electron donor.…”

Dendritic Polyglycerol‐Derived Nano‐Architectures as Delivery Platforms of Gemcitabine for Pancreatic Cancer

“…Our hypothesis was based on the fact that such programmed disintegration of larger nanoparticles will provide with deeper penetration of drug‐transporting nanocarriers through the dense desmoplastic microenvironment of pancreatic cancer. We selected pH as the stimulus to trigger such controlled destabilization because for PDAC and any other form of solid tumors, pH decreases sharply in conjunction with low O 2 tension as the distance increases from blood vessels to tumor tissues . In addition, smaller nanoparticles are required to penetrate deep‐seated tumor cells and cancer‐like stem cells, many of which are difficult to reach with larger nanoparticles due to altered microvasculature present in solid tumors.…”

Biomimetic, Hypoxia‐Responsive Nanoparticles Overcome Residual Chemoresistant Leukemic Cells with Co‐Targeting of Therapy‐Induced Bone Marrow Niches

“…The hypoxia‐responsive release of aTGFβRII was evaluated according to the method previously described . Briefly, 0.35 mL A azo @CMSN aqueous solution (5 mg mL −1 ) were placed in Eppendorf tubes followed by adding 50 µL PBS (0.1 m ), 30 µL rat liver microsomes, and 70 µL NADPH (2 × 10 −3 m ).…”