Tumor Microenvironment Adaptable Nanoplatform for O₂ Self‐Sufficient Chemo/Photodynamic Combination Therapy

Abstract

Malignant proliferation of tumor cells induces abnormal tissue microenvironments, leading to therapeutic resistance and poor therapeutic outcome. In this paper, manganese dioxide (MnO2) nanoshells are coated on a porphyrinic metal–organic framework of porous coordination network (PCN)‐224 for doxorubicin (DOX) loading and hyaluronic acid (HA) modification to obtain an intelligent nanoplatform of PCN@MnO2@DOX@HA (PMDH). Benefiting from the HA functionalization, PMDH prefers to accumulate in tumor sites and enhance the cellular uptake by CD44‐overexpressed tumor cells. Subsequently, the internalized PMDH could catalyze the abundant H2O2 in cells into O2 to relieve tumor hypoxia. Further, the MnO2 nanoshells of PMDH could be degraded into Mn2+ for magnetic resonance imaging with glutathione reduction and the release of DOX. By integrating the O2 self‐sufficiency with glutathione reduction abilities, PMDH possesses highly potent chemo/photodynamic combination therapeutic effects against hypoxic tumors. Significantly, PMDH exhibits a good biocompatibility with a low cardiotoxicity and negligible systemic side effects, which provides a new insight in developing tumor microenvironment adaptable nanoplatforms for synergistic tumor theranostics.

Recent Advances in Strategies for Addressing Hypoxia in Tumor Photodynamic Therapy

“…Among the metal-based materials for generating oxygen through H 2 O 2 decomposition, MnO 2 is a widely studied material [ 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 ]. MnO 2 could produce oxygen and Mn 2+ at acidic pH, particularly in the presence of H 2 O 2 .…”

Recent Advances in Metal–Organic Frameworks for Applications in Magnetic Resonance Imaging

“…Due to the high r 2 /r 1 ratio ( > 15), the nanoparticles could be assigned as a T 2 -dominated contrast agent. Zhang et al reported on integrating Gd-doped silica nanoparticles within a MOF ZIF-8, which was loaded with chlorin e6 and doxorubicin (anticancer drug) in order to prepare an agent for drug delivery, and bimodal MR and fluorescent imaging . Moreover, the particle surface was functionalized with folic acid to enable tumor targeted delivery.…”

“…The r 1 relaxivity at pH 6.5 in the presence of H 2 O 2 was determined to be 6.59 mM –1 s –1 (at 1.5 T). In another work, porphyrin-based MOF nanoparticles coated with a MnO 2 shell were used for drug delivery of doxorubicin and T 1 -MRI . MR imaging of nanoparticles treated with GSH or incubated in buffer solutions with different pH values was performed.…”

Polysaccharide-Based Theranostic Systems for Combined Imaging and Cancer Therapy: Recent Advances and Challenges

“…To further explore the potential of MOF-based theranostics for multimodal imaging and drug delivery, Lin et al designed carbon dots embedded MOF@O-carboxymethyl chitosan nanoparticles. 92 The use of O-carboxymethyl chitosan in fabricating the particles provided pH-responsive release of doxorubicin. The developed system could be used for dualimaging including fluorescence and T 2 MRI.…”

“…The developed nanocomposite acted as a robust theranostic system exhibiting controlled release of both curcumin and 5-FU along with enhanced T 2 MRI contrast in cancer cells. To further explore the potential of MOF-based theranostics for multimodal imaging and drug delivery, Lin et al designed carbon dots embedded MOF@O-carboxymethyl chitosan nanoparticles . The use of O -carboxymethyl chitosan in fabricating the particles provided pH-responsive release of doxorubicin.…”