Multifunctional Hollow MnO₂@Porphyrin@Bromelain Nanoplatform for Enhanced Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) has been showing great potential in cancer treatment. However, the efficacy of PDT is always limited by the intrinsic hypoxic tumor microenvironment (TME) and the low accumulation efficiency of photosensitizers in tumors. To address the issue, a multifunctional hollow multilayer nanoplatform (H‐MnO2@TPyP@Bro) comprising manganese dioxide, porphyrin (TPyP) and bromelain (Bro), is developed for enhanced photodynamic therapy. MnO2 catalyzes the intracellular hydrogen peroxide (H2O2) to produce oxygen (O2), reversing the hypoxic TME in vivo. The generated O2 is converted into singlet oxygen (1O2) by the TPyP shell under near‐infrared light, which can inhibit tumor proliferation. Meanwhile, the Bro can digest collagen in the extracellular matrix around the tumor, and can promote the accumulation of H‐MnO2@TPyP@Bro in the deeper tumor tissue, further improving the therapeutic effect of PDT. In addition, MnO2 can react with the overexpressed glutathione in TME to release Mn2+. Consequently, Mn2+ not only induces chemo‐dynamic therapy based on Fenton reaction by converting H2O2 into hydroxyl radicals, but also activates the Mn2+‐based magnetic resonance imaging. Therefore, the developed H‐MnO2@TPyP@Bro nanoplatform can effectively modulate the unfavorable TME and overcome the limitations of conventional PDT for cancer diagnostic and therapeutic.

Nanotechnological strategies to increase the oxygen content of the tumor

“…However, the previously reported structures of MnO 2 are mostly nanoparticles, nanocomposites in combination with other types of nanoparticles or nanosheets, which may not be ideal for the effective loading and accurate release of drugs. Hollow nanostructures have been shown to be able to construct loading/delivery nanoplatforms for the precisely controlled release of therapeutic agents ( Zhang et al, 2022f ; Zhu et al, 2022 ). The research group of Liu developed a biodegradable hollow MnO 2 nanotherapeutic ( Figure 4B ) ( Yang et al, 2017 ).…”

Multifunctional nanomedicines-enabled chemodynamic-synergized multimodal tumor therapy via Fenton and Fenton-like reactions

“…We will show the representative examples of CDT/chemotherapy, CDT in combination with therapies based on external stimuli (light, ultrasound, x-rays, magnet) and chemical and biological stimuli (immunization, nutrition, gas, gene silencing, bioactive ions) for synergistic enhancement (Table 2). H-MnO2@TPyP@Bro Hollow sphere, 240 MCF-7 MCF-7 20% (300) Producing O2, Bro promotes the accumulation of H-MnO2@TPyP@Bro [77], 2022 4-DCF-MPYM Cu 2+ CaO2-FM@Cu-ONS@HC Sphere, 120.4 HeLa, 4T1, COS-7 4T1 10% (100) O2/H2O2 self-sufficient [78], 2022…”

“…Based on this, various reagents for O2 release and GSH consumption have been developed [75,76]. In order to improve the enrichment of photosensitizers in the deep tumor and ameliorate the hypoxia of the TME, a multifunctional hollow PDT nanoplatform (H-MnO2@TPyP@Bro) composed of MnO2, porphyrin (TPyP) and bromelain (Bro) was successfully designed [77]. In this system, Bro digested collagen, thereby enhancing H-MnO2@TPyP@Bro enrichment in deeper areas of the tumor.…”

Delivery of miR‐3529‐3p using MnO2‐SiO2‐APTES nanoparticles combined with phototherapy suppresses lung adenocarcinoma progression by targeting HIGD1A

“…In the instance of non‐small lung carcinoma diagnosis, application of MnO 2 improved magnetic resonance (MR) imaging outcomes 2,20 . Moreover, MnO 2 nanostructures have been demonstrated to reduce tumor hypoxia by triggering the decomposition of endogenous H 2 O 2 into oxygen and Mn 2+ , thereby significantly improving the treatment outcomes of reactive oxygen species (ROS) mediated tumor therapy 21,22 . In addition, Mn 2+ has also been verified to inhibit tumor growth by generating ROS through fenton reaction with H 2 O 2 in tumor tissues 23 .…”

“… 2 , 20 Moreover, MnO 2 nanostructures have been demonstrated to reduce tumor hypoxia by triggering the decomposition of endogenous H 2 O 2 into oxygen and Mn 2+ , thereby significantly improving the treatment outcomes of reactive oxygen species (ROS) mediated tumor therapy. 21 , 22 In addition, Mn 2+ has also been verified to inhibit tumor growth by generating ROS through fenton reaction with H 2 O 2 in tumor tissues. 23 Recently, MnO 2 nanosheets have been shown to act as a photothermal agent for PTT, mainly because of their oxygen vacancy structure.…”