Cancer Cell Membrane‐Biomimetic Oxygen Nanocarrier for Breaking Hypoxia‐Induced Chemoresistance

Abstract

The inadequate oxygen supply in solid tumor causes hypoxia, which leads to drug resistance and poor chemotherapy outcomes. To solve this problem, a cancer cell membrane camouflaged nanocarrier is developed with a polymeric core encapsulating hemoglobin (Hb) and doxorubicin (DOX) for efficient chemotherapy. The designed nanoparticles (DHCNPs) retain the cancer cell adhesion molecules on the surface of nanoparticles for homologous targeting and possess the oxygen-carrying capacity of Hb for O 2 -interfered chemotherapy. The results show that DHCNPs not only achieve higher tumor specificity and lower toxicity by homologous targeting but also significantly reduce the exocytosis of DOX via suppressing the expressions of hypoxia-inducible factor-1α, multidrug resistance gene 1, and P-glycoprotein, thus resulting in safe and high-efficient chemotherapy. This work presents a new paradigm for targeted oxygen interference therapy by conquering hypoxia-involved therapeutic resistance and achieves effective treatment of solid tumors.

Cancer Cell Membrane-Coated Nanoparticles for Cancer Management

“…By suppressing the expression of hypoxia-inducible factor-1α, multidrug resistance gene 1, and P-glycoprotein, the biomimetic oxygen nanocarriers were able to perform safe and highly efficient O2-interfered chemotherapy by reducing the exocytosis of DOX. Simultaneously, the system achieved higher tumor specificity and lower DOX toxicity due to the cancer cell adhesion molecules retained on the NP surface [63]. This was an excellent demonstration of the potential for CCNPs to achieve multi-therapeutic delivery.…”

“…This will facilitate proper orientation of the membrane around the NP owing to electrostatic repulsion between the NP surface and negative extracellular membrane components [27]. To date, the types of synthetic NPs that have been wrapped with cell-derived membranes for cancer therapies include nanocrystals [54], nanocages [42], mineral-based or mesoporous silica [35,49,[55][56][57][58], polymeric cores [30,40,45,[59][60][61][62][63][64], organic and inorganic metal frameworks [44,51,[65][66][67], protein cores [68,69], and gold-based or magnetic nanoparticles [70][71][72] (Figure 4, Table 1). Poly(lactic-co-glycolic) acid (PLGA) is one of the most widely used NP cores due to its biodegradability, FDA approval, and ability to encapsulate many products [17][18][19].…”

“…DOX has been used clinically to treat many cancers, including breast cancer, ovarian cancer, and various lymphomas and leukemias [78]. Several researchers have shown that encapsulating DOX in membrane-wrapped NPs is advantageous compared to freely delivered DOX [56,62,63]. For example, Xu et al developed PLGA-DOX NPs wrapped in membranes derived from HepG2 hepatocarcinoma cells and showed these NPs could deliver an effective drug payload to Hep2G tumors in mice [62].…”

“…This ensures the cargos are delivered to the same cells within tumor sites for improved anticancer effects. This was demonstrated with PLGA cores that were loaded with hemoglobin (Hb) and DOX and coated with MCF-7 human breast cancer cell membranes with a PEGylated phospholipid to overcome hypoxia-induced chemoresistance [63]. By suppressing the expression of hypoxia-inducible factor-1α, multidrug resistance gene 1, and P-glycoprotein, the biomimetic oxygen nanocarriers were able to perform safe and highly efficient O2-interfered chemotherapy by reducing the exocytosis of DOX.…”

“…CCNPs that incorporate stimuli-responsive features have also been designed to take advantage of the acidic tumor microenvironment as a trigger for localized drug release [63]. In one example, mesoporous silica nanoparticle (MSN) cores were used to encapsulate DOX with the addition of a unique CaCO3 interlayer [56].…”