Cancer Cell Membrane Camouflaged Cascade Bioreactor for Cancer Targeted Starvation and Photodynamic Therapy

Abstract

Selectively cuting off the nutrient supply and the metabolism pathways of cancer cells would be a promising approach to improve the efficiency of cancer treatment. Here, a cancer targeted cascade bioreactor (designated as mCGP) was constructed for synergistic starvation and photodynamic therapy (PDT) by embedding glucose oxidase (GOx) and catalase in the cancer cell membrane-camouflaged porphyrin metal-organic framework (MOF) of PCN-224 (PCN stands for porous coordination network). Due to biomimetic surface functionalization, the immune escape and homotypic targeting behaviors of mCGP would dramatically enhance its cancer targeting and retention abilities. Once internalized by cancer cells, mCGP was found to promote microenvironmental oxygenation by catalyzing the endogenous hydrogen peroxide (HO) to produce oxygen (O), which would subsequently accelerate the decomposition of intracellular glucose and enhance the production of cytotoxic singlet oxygen (O) under light irradiation. Consequently, mCGP displayed amplified synergistic therapeutic effects of long-term cancer starvation therapy and robust PDT, which would efficiently inhibit the cancer growth after a single administration. This cascade bioreactor would further facilitate the development of complementary modes for spatiotemporally controlled cancer treatment.

Chemotaxis-driven delivery of nano-pathogenoids for complete eradication of tumors post-phototherapy

“…A number of studies have reported the successful use of phototherapy, such as PTT and photodynamic therapy (PDT), in the treatment of cancers [41][42][43][44][45][46] . In our study, PTT only moderately delayed the tumor growth.…”

Innovative Strategies for Hypoxic‐Tumor Photodynamic Therapy

“…[44,45] Because of these combined observations,m any nano-platforms for PDT have been designed to contain catalase to transform endogenous H 2 O 2 to O 2 . [46][47][48] In 2015, Chen et al constructed aH 2 O 2 -responsive and O 2 -evolving nanocomposite for use in highly selective PDT to overcome tumor hypoxia. [46] In this nanocomposite,c atalase and the PS,m ethylene blue,w ere co-encapsulated into the aqueous core,a nd the quencher,B HQ-3 was doped into the polymeric shell that also contained the cancer cell-targeting group,c (RGDfK).…”

“…Overall, as compared to traditional PSs this innovative nano-PS system enables more efficient and precise PDT against hypoxic tumors.Z hangsg roup also developed two other catalase-containing, cell membrane-coated nanoplatforms for O 2 -elevating PDT. [47,48] In addition to catalase,s everal other nanomaterials,s uch as MnO 2 nanoparticles,g old nanoclusters,p latinum nanozymes,a nd mesoporous cerium oxide hollow nanoparticles, have been used in PDT-related systems to catalyze the transformation of H 2 O 2 to O 2 . [49][50][51][52][53][54][55] Fore xample,L in et al recently fabricated ac atalase-like nanocomposite containing MnO 2 and chlorin e6 by using human serum albumin as the building block.…”

Insight into the efficiency of oxygen introduced photodynamic therapy (PDT) and deep PDT against cancers with various assembled nanocarriers

“…Thus, the efficiency of PDT could be dramatically improved (Phua et al, ). Zhang's group developed cell‐like biomimetic nanoplatform for O 2 self‐sufficient PDT (Cheng et al, ; Li et al, ). Glucose oxidase and catalase were loaded by PS nanoparticles, and then covered by cancer cell membrane.…”

“…The cascade bioreactor could decompose endogenous H 2 O 2 and intracellular glucose, which not only improved the hypoxia of tumors, but also induced cancer starvation. The synergistic effects of starvation therapy and PDT could effectively inhibit the tumor growth (Li, Cheng, et al, ). Liu's group also designed several catalase conjugated PSs to increase the O 2 concentration of tumors to increase PDT efficiency (Chen et al, ; Meng et al, ; Wang et al, ).…”