Asplatin, a fusion of aspirin and cisplatin, exhibits significant cytotoxicity in tumor cells and almost fully overcomes the drug resistance of cisplatin resistant cells. Asplatin is highly accumulated in cancer cells and is activated upon the reduction by ascorbic acid.
The
combination of photodynamic therapy (PDT) and enzyme therapy
is a highly desirable approach in malignant tumor therapies as it
takes advantage of the spatial-controlled PDT and the effective enzyme-catalyzed
bioreactions. However, it is a challenge to co-encapsulate hydrophilic
enzymes and hydrophobic photosensitizers, and these two agents often
interfere with each other. In this work, a protocell-like nanoreactor
(GOx-MSN@MnPc-LP) has been designed for synergistic starvation therapy
and PDT. In this nanoreactor, the hydrophilic glucose oxidase (GOx)
is loaded in the pore of mesoporous silica nanoparticles (MSNs), while
the hydrophobic manganese phthaleincyanide (MnPc) is loaded in the
membrane layer of liposome. This spatial separation of two payloads
protects GOx and MnPc from the cellular environment and avoids interference
with each other. GOx catalyzes the oxidation of glucose, which generates
hydrogen peroxide and gluconic acid, leading to the starvation therapy
via glucose consumption in cancer cells, as well as the disruption
of cellular redox balance. MnPc produces cytotoxic singlet oxygen
under 730 nm laser irradiation, achieving PDT. The antitumor effects
of the nanoreactor have been verified on tumor cells and tumor-bearing
mice models. GOx-MSN@MnPc-LP efficiently inhibits tumor growth in vivo with a single treatment, indicating the robust synergy
of starvation therapy and PDT treatment. This work also offers a versatile
strategy for delivering hydrophilic enzymes and hydrophobic photosensitizers
using a protocell-like nanoreactor for effective cancer treatment.
Polyplex micelles were constructed for deep tumor tissue penetration and combating drug resistance via endogenous stimuli-responsive two-step release profiles.
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