Designer particles that are embued with nanomachinery for autonomous motion have great potential for biomedical applications; however, their development is highly demanding with respect to biodegradability/compatibility. Previously, biodegradable propulsive machinery based on enzymes has been presented. However, enzymes are highly susceptible to proteolysis and deactivation in biological milieu. Biodegradable hybrid nanomotors powered by catalytic inorganic nanoparticles provide a proteolytically stable alternative to those based upon enzymes. Herein we describe the assembly of hybrid biodegradable nanomotors capable of transducing chemical energy into motion. Such nanomotors are constructed through a process of compartmentalized synthesis of inorganic MnO 2 nanoparticles (MnPs) within the cavity of organic stomatocytes. We show that the nanomotors remain active in cellular environments and do not compromise cell viability. Effective tumor penetration of hybrid nanomotors is also demonstrated in proof-of-principle experiments. Overall, this work represents a new prospect for engineering of nanomotors that can retain their functionality within biological contexts.

Photodynamic therapy (PDT) is an effective noninvasive therapeutic method that employs photosensitizers (PSs) converting oxygen to highly cytotoxic singlet oxygen ( 1 O 2 ) under light irradiation. The conventional PDT efficacy is, however, compromised by the nonspecific delivery of PSs to tumor tissue, the hypoxic tumor microenvironment, and the reduction of generated 1 O 2 by the intracellular antioxidant glutathione (GSH). Herein, an intelligent multifunctional synergistic nanoplatform (CMGCC) for T 1 -weighted magnetic resonance (MR) imaging-guided enhanced PDT is presented, which consists of nanoparticles composed of catalase (CAT) and manganese dioxide (MnO 2 ) that are integrated within chlorin-e6-modified glycol chitosan (GC) polymeric micelles. In this system, (1) GC polymers with pH-sensitive surface charge switchability from neutral to positive could improve the PS accumulation within the tumor region, (2) CAT could effectively reoxygenate the hypoxic tumor via catalyzing endogenous hydrogen peroxide to O 2 , and (3) MnO 2 could consume the intracellular GSH while simultaneously producing Mn 2+ as a contrast agent for T 1 -weighted MR imaging. The CMGCC particles possess uniform size distribution, well-defined structure, favorable enzyme activity, and superior 1 O 2 generation ability. Both in vitro and in vivo experiments demonstrate that the CMGCC exhibit significantly enhanced PDT efficacy toward HeLa cells and subcutaneous HeLa tumors. Our study thereby demonstrates this to be a promising synergistic theranostic nanoplatform with highly efficient PDT performance for cancer therapy.

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We report the facile synthesis of polyaniline (PANI)-loaded γ-polyglutamic acid (γ-PGA) nanogels (NGs) for photoacoustic (PA) imaging-guided photothermal therapy (PTT) of tumors. In this work, γ-PGA NGs were first formed via a double emulsion approach, followed by crosslinking with cystamine dihydrochloride (Cys) via 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride coupling chemistry. The formed γ-PGA/Cys NGs were employed as a nanoreactor to load aniline monomers via an electrostatic interaction for subsequent in situ polymerization in the presence of ammonium persulfate. The resulting γ-PGA/Cys@PANI NGs were thoroughly characterized. It is shown that the γ-PGA/Cys@PANI NGs with an average size of 71.9 nm are dispersible in water, colloidally stable, and cytocompatible and hemocompatible in the concentration range studied. The strong near-infrared (NIR) absorbance renders the NGs with good PA imaging contrast enhancement and photothermal conversion properties. With these excellent properties and biocompatibility, the developed γ-PGA/Cys@PANI NGs are able to be used for PA imaging-guided PTT of cancer cells in vitro and a xenografted tumor model in vivo. This unique theranostic nanoplatform may be further loaded with other imaging or therapeutic elements, or modified with targeting ligands, thereby providing a ubiquitous platform for multimode imaging and combinational therapy of different biosystems.