Facile Phototherapeutic Nanoplatform by Integrating a Multifunctional Polymer and MnO₂ for Enhancing Tumor Synergistic Therapy

Abstract

of tumor. [7][8][9] Thus, SPT could exhibit the synergistic effect of "1 + 1 > 2" in theory. However, the effect of PDT would be limi ted severely due to the hypoxic microen vironment in the tumor, leading to that the photothermal effect often dominates the therapy efficiency during the syner gistic therapy process. [10][11][12][13][14][15][16] Thus, tradi tional combination of PTT and PDT failed to fully perform the effect of synergistic phototherapy. Consequently, it is very urgent to develop novel SPT agents which can show the truly synergistic and even enhanced effects of PTT and PDT.Recent works indicated that MnO 2 is a versatile nanocarrier for anticancer treat ment. [13][14][15][16][17] MnO 2 nanostructures have been demonstrated to enhance the anti cancer efficiency through the following three approaches: (1) catalyzing H 2 O 2 to generate O 2 to relieve the hypoxic environ ment in the tumor and enhance the PDT effect, [17,18] (2) generating extra heat to improve the PTT efficiency under irradia tion, [10,21] and (3) reacting with glutathione to reduce the consumption of ROS and release the anticancer drug to enhance the synergistic therapy process. [19,20] Therefore, MnO 2 nanocarriers provide a new insight into design strategies for enhancement of SPT effect. Nevertheless, common strategies to utilize MnO 2 nanocarrier for improving the anticancer effects face with the problems of complicated structures and cumbersome preparation process, because the nanosystems usually contain MnO 2 nanocarrier with various morphologies, phototherapy agents, hydrophilic group, and even some functional groups such as protein and RNA. [21][22][23][24] Therefore, developing MnO 2 nanosystems with simple structures for enhancing the synergistic therapeutic effi ciency is urgent but challenging.In order to construct a simple MnO 2 based nanosystem to realize the truly synergistic and even enhanced effects of PTT and PDT, suitable phototherapeutic agents should be selected. Among numerous phototherapeutic agents, nearinfrared (NIR) azaBODIPY dyes, which exhibit both excellent photo thermal and photodynamic effects, were ideal SPT agent for further application in combination with MnO 2 . [25][26][27][28][29] In parallel, to avoid the complex structure and preparation process of the Recent studies indicate that the synergistic phototherapy (SPT) process can simultaneously generate heat for photothermal therapy (PTT) and singlet oxygen ( 1 O 2 ) for photodynamic therapy (PDT) to overcome the recurrence of tumors. However, the hypoxic environment in tumors seriously limits the therapeutic effect of the oxygen-dependent PDT, leading to the domination of PTT in the SPT process. Therefore, it is urgent to develop a novel SPT platform for overcoming hypoxia in tumors and improving the therapeutic effect of both PTT and PDT. In this work, a novel phototherapeutic platform based on a nanocomposite of aza-BODIPY/manganese dioxide (MnO 2 ) is developed via simple electrostatic self-assembly. In this design, MnO 2 nanosheets, which coul...

A chemical biology toolbox to overcome the hypoxic tumor microenvironment for photodynamic therapy: a review

“…The root cause of tumor tissue hypoxia is that the disordered proliferation of tumor cells consumes a large amount of oxygen. 60 Therefore, to fundamentally solve the problem of tumor hypoxia, we should start with the endogenous problem and inhibit tumor cell respiration.…”

Green Layer-by-Layer Assembly of Porphyrin/G-Quadruplex-Based Near-Infrared Nanocomposite Photosensitizer with High Biocompatibility and Bioavailability

“…Otherwise, the bioavailability of photosensitizers might be greatly reduced. Last but not least, some photosensitizer molecules are deeply encapsulated in the interior of nanocarriers; they cannot make a contribution to PDT performance even though they may also produce 1 O 2 under the irradiation of excitation light since the generated 1 O 2 is even unable to reach the target organelles due to its limited lifetime and short diffusion distance (∼100 nm). − Therefore, developing a facile and green strategy for fabricating highly biocompatible nanocarriers that can achieve highly efficient delivery and utilization of photosensitizers is still urgently in demand. − …”

NIR-Driven Intracellular Photocatalytic O2 Evolution on Z-Scheme Ni3S2/Cu1.8S@HA for Hypoxic Tumor Therapy

“…However, the O 2 dissolution and release from PFC is determined by its partial pressure, and a leak is also difficult to avoid. − In addition, the catalase or MnO 2 nanomaterials were adopted to convert the endogenous H 2 O 2 , creating in situ O 2 production. Nevertheless, the limited intracellular H 2 O 2 content restricted their development. − Moreover, some ferrates also have been tried to be used, but their excessive reactivity also requires a tedious assembly process . Therefore, an ingenious nanocomposite is desired to offer the controlled, safe, and high performance for an O 2 supplement in a tumor cell that would improve PDT as well.…”