Oxygen‐Evolving Manganese Ferrite Nanovesicles for Hypoxia‐Responsive Drug Delivery and Enhanced Cancer Chemoimmunotherapy

Abstract

Immunological tolerance induced by the hypoxic tumor microenvironment has been a major challenge for current immune checkpoint blockade therapies. Here, a hypoxia‐responsive drug delivery nanoplatform is reported to promote chemoimmunotherapy of cancer by overcoming the hypoxia‐induced immunological tolerance of tumors. The nanovesicles are assembled from manganese ferrite nanoparticles (MFNs) grafted with hypoxia‐responsive amphiphilic polymers as the membrane, with doxorubicin hydrochloride (Dox) loaded in the aqueous cavities. Under hypoxic conditions in tumors, the nanovesicles can rapidly dissociate into individual MFNs to release Dox and induce decomposition of tumor endogenous H2O2 for tumor hypoxia relief. As a result, the Dox‐loaded nanovesicles display remarkable suppression of primary tumor growth in combination with αPD‐L1‐mediated checkpoint blockade therapy. Furthermore, the modulation of the hypoxic tumor microenvironment facilitates a long‐lasting immunological memory effect to prevent tumor recurrence and metastasis. Therefore, this hypoxia‐responsive nanoplatform presents a potential strategy for both local tumor treatment and long‐term protection against tumor recurrence.

Tumor‐Microenvironment‐Responsive Nanomedicine for Enhanced Cancer Immunotherapy

“…In combination with PD‐L1‐mediated checkpoint blockade therapy, the nanomedicine not only achieved a superior effect to suppress the growth of the primary tumor, but also promoted long‐lasting immune memory to inhibit tumor recurrence and metastasis (Figure 6l,m ). [ 72 ]…”

“…Reproduced with permission. [ 72 ] Copyright 2021, Wiley‐VCH. p ‐Values: * p < 0.05; ** p < 0.01; *** p < 0.001.…”

“…l,m) Cytokine levels in the sera from mice isolated 7 days after mice were rechallenged with secondary tumors (on day 47). Reproduced with permission [72]. Copyright 2021, Wiley-VCH.…”

ROS‐Catalytic Transition‐Metal‐Based Enzymatic Nanoagents for Tumor and Bacterial Eradication

“…[11,[37][38][39][40][41] But almost no review has focused on the design, fundamental principles, augmenting factors, and material chemistries in developing and applications of TM-based EnzNAs. [27,[42][43][44][45] Herein, as shown in Scheme 1, this timely review provides the most recent advances for the construction of TM-EnzNA and ROS-based strategies to kill pathogenic cells, especially the eradication of tumors and bacteria. At first, the different ROSproducing mechanisms and the key factors (including H 2 O 2 , sonostimulation, photostimulation, and X-ray stimulation) to enhance ROS level are carefully concluded, as well as the analytic methods are systematically summarized.…”

Confinement Assembly in Polymeric Micelles Enables Nanoparticle Superstructures with Tunable Molecular‐Like Geometries

“…[ 1 ] In particular, the assembly of finite NPs into small clusters that mimic the structure and geometry of molecules—i.e., colloidal molecules—provides an elegant route for creating intended superstructures with programmable architectures. [ 2 ] Technologically, such as NP clusters (NPCs) are important for their proposed applications in drug delivery, [ 3 ] photodynamic therapy, [ 4 ] and plasmonics, [ 5 ] due to their precisely tunable geometry and unique ensemble effect. Fundamentally, NPCs can serve as model systems to elucidate the phase behavior and assembly kinetics of extended NP superstructures such as 3D superlattices, as it has been hypothesized that NPs might preassemble into clusters along the path toward forming the final superlattices.…”