Chemodynamic therapy (CDT) utilizes iron‐initiated Fenton chemistry to destroy tumor cells by converting endogenous H2O2 into the highly toxic hydroxyl radical (.OH). There is a paucity of ...Fenton‐like metal‐based CDT agents. Intracellular glutathione (GSH) with .OH scavenging ability greatly reduces CDT efficacy. A self‐reinforcing CDT nanoagent based on MnO2 is reported that has both Fenton‐like Mn2+ delivery and GSH depletion properties. In the presence of HCO3−, which is abundant in the physiological medium, Mn2+ exerts Fenton‐like activity to generate .OH from H2O2. Upon uptake of MnO2‐coated mesoporous silica nanoparticles (MS@MnO2 NPs) by cancer cells, the MnO2 shell undergoes a redox reaction with GSH to form glutathione disulfide and Mn2+, resulting in GSH depletion‐enhanced CDT. This, together with the GSH‐activated MRI contrast effect and dissociation of MnO2, allows MS@MnO2 NPs to achieve MRI‐monitored chemo–chemodynamic combination therapy.
Self‐reinforcing weapon: The Fenton‐like Mn2+ delivery and glutathione (GSH) depletion abilities of MnO2 allow it to exert enhanced chemodynamic efficacy in cancer treatment. An activatable theranostic platform based on multifunctional MnO2‐coated mesoporous silica nanoparticles (MS@MnO2 NPs) has been developed for MRI‐monitored combination chemotherapy and chemodynamic therapy (CDT). ADS=antioxidant defense system.
Reactive oxygen species (ROS) can be used not only as a therapeutic agent for chemodynamic therapy (CDT), but also as a stimulus to activate release of antitumor drugs, achieving enhanced efficacy ...through the combination of CDT and chemotherapy. Here we report a pH/ROS dual‐responsive nanomedicine consisting of β‐lapachone (Lap), a pH‐responsive polymer, and a ROS‐responsive polyprodrug. In the intracellular acidic environment, the nanomedicine can realize pH‐triggered disassembly. The released Lap can efficiently generate hydrogen peroxide, which will be further converted into highly toxic hydroxyl radicals via the Fenton reaction. Subsequently, through ROS‐induced cleavage of thioketal linker, doxorubicin is released from the polyprodrug. In vivo results indicate that the cascade of ROS generation and antitumor‐drug release can effectively inhibit tumor growth. This design of nanomedicine with cascade reactions offers a promising strategy to enhance antitumor efficacy.
Cascade reactions: A nanomedicine that consists of a pH‐responsive polymer and polyprodrug, which is responsive to reactive oxygen species (ROS), has been developed. This nanomedicine can achieve enhanced antitumor efficacy by the cascade of ROS generation and drug release, which is promising for chemo/chemodynamic combination cancer therapy.
Cell membrane coating nanotechnology, which endows nanoparticles with unique properties, displays excellent translational potential in cancer diagnosis and therapy. However, the preparation and ...evaluation of these cell membrane‐coated nanoparticles are based on cell lines and cell‐line‐based xenograft mouse models. The feasibility of cell membrane‐camouflaged nanomaterials is tested in a preclinical setting. Head and neck squamous cell carcinoma (HNSCC) patient‐derived tumor cell (PDTC) membranes are coated onto gelatin nanoparticles (GNPs) and the resulting PDTC@GNPs show efficient targeting to homotypic tumor cells and tissues in patient‐derived xenograft (PDX) models. When the donor‐derived cell membrane of PDTC@GNPs matched those of the host cells, significant targeting capability is observed. In contrast, mismatch between the donor and host results in weak targeting. Furthermore, it is demonstrated that autologous separation and administration of cellular membranes and anticancer cisplatin (Pt)‐loaded PDTC@GNPs, respectively, lead to almost complete tumor ablation in a subcutaneous model and effectively inhibit tumor recurrence in a postsurgery model. The work presented here reinforces the translation of these biomimetic nanoparticles for clinical applications and offers a simple, safe, and effective strategy for personalized cancer treatment.
Cancer cell membrane‐coated nanoparticles, which inherit homologous cancer targeting capability from the source cells, are used for personalized cancer treatment in patient‐derived xenograft models. This represents a simple, safe, and effective strategy for personalized cancer treatment.
Yolk–shell nanostructures (YSNs) composed of a core within a hollow cavity surrounded by a porous outer shell have received tremendous research interest owing to their unique structural features, ...fascinating physicochemical properties, and widespread potential applications. Here, a comprehensive overview of the design, synthesis, and biomedical applications of YSNs is presented. The synthetic strategies toward YSNs are divided into four categories, including hard‐templating, soft‐templating, self‐templating, and multimethod combination synthesis. For the hard‐ or soft‐templating strategies, different types of rigid or vesicle templates are used for making YSNs. For the self‐templating strategy, a number of unconventional synthetic methods without additional templates are introduced. For the multimethod combination strategy, various methods are applied together to produce YSNs that cannot be obtained directly by only a single method. The biomedical applications of YSNs including biosensing, bioimaging, drug/gene delivery, and cancer therapy are discussed in detail. Moreover, the potential superiority of YSNs for these applications is also highlighted. Finally, some perspectives on the future research and development of YSNs are provided.
Yolk–shell nanostructures (YSNs) attract increasing attention because of their unique structural features, fascinating physicochemical properties, and widespread potential applications. Various strategies for the fabrication of yolk–shell nanostructures, such as hard‐, soft‐, and self‐templating and multimethod combination synthesis, are discussed in detail. The biomedical applications of YSNs including biosensing, bioimaging, drug/gene delivery, and cancer therapy are also presented.
Nanomedicines have been demonstrated to have passive or active tumor targeting behaviors, which are promising for cancer chemotherapy. However, most nanomedicines still suffer from a suboptimal ...targeting effect and drug leakage, resulting in unsatisfactory treatment outcome. Herein, a hierarchical responsive nanomedicine (HRNM) is developed for programmed delivery of chemotherapeutics. The HRNMs are prepared via the self‐assembly of cyclic Arg‐Gly‐Asp (RGD) peptide conjugated triblock copolymer, poly(2‐(hexamethyleneimino)ethyl methacrylate)‐poly(oligo‐(ethylene glycol) monomethyl ether methacrylate)‐polyreduction‐responsive camptothecin (PC7A‐POEG‐PssCPT). In blood circulation, the RGD peptides are shielded by the POEG coating; therefore, the nanosized HRNMs can achieve effective tumor accumulation through passive targeting. Once the HRNMs reach a tumor site, due to the hydrophobic‐to‐hydrophilic conversion of PC7A chains induced by the acidic tumor microenvironment, the RGD peptides will be exposed for enhanced tumor retention and cellular internalization. Moreover, in response to the glutathione inside cells, active CPT drugs will be released rapidly for chemotherapy. The in vitro and in vivo results confirm effective tumor targeting, potent antitumor effect, and reduced systemic toxicity of the HRNMs. This HRNM is promising for enhanced chemotherapeutic delivery.
A hierarchical responsive nanomedicine, which can achieve programmed targeting and triggered drug release, is developed for enhanced chemotherapeutic delivery. In physiological conditions, the nanomedicine shows high stability without obvious drug leakage. Once reaching the tumor microenvironment, the activated RGD peptides can achieve enhanced cellular uptake. Then, active camptothecin moieties are rapidly released in response to the intracellular glutathione.
Multifunctional nanocomposites have the potential to integrate sensing, diagnostic, and therapeutic functions into a single nanostructure. Herein, we synthesize Fe3O4@polydopamine core–shell ...nanocomposites (Fe3O4@PDA NCs) through an in situ self-polymerization method. Dopamine, a melanin-like mimic of mussel adhesive proteins, can self-polymerize to form surface-adherent polydopamine (PDA) films onto a wide range of materials including Fe3O4 nanoparticles used here. In such nanocomposites, PDA provides a number of advantages, such as near-infrared absorption, high fluorescence quenching efficiency, and a surface for further functionalization with biomolecules. We demonstrate the ability of the Fe3O4@PDA NCs to act as theranostic agents for intracellular mRNA detection and multimodal imaging-guided photothermal therapy. This work would stimulate interest in the use of PDA as a useful material to construct multifunctional nanocomposites for biomedical applications.
Single molecular nanoparticles (SMNPs) integrating imaging and therapeutic capabilities exhibit unparalleled advantages in cancer theranostics, ranging from excellent biocompatibility, high ...stability, prolonged blood lifetime to abundant tumor accumulation. Herein, we synthesize a sophisticated porphyrin nanocage that is further functionalized with twelve polyethylene glycol arms to prepare SMNPs (porSMNPs). The porphyrin nanocage embedded in porSMNPs can be utilized as a theranostic platform. PET imaging allows dynamic observation of the bio‐distribution of porSMNPs, confirming their excellent circulation time and preferential accumulation at the tumor site, which is attributed to the enhanced permeability and retention effect. Moreover, the cage structure significantly promotes the photosensitizing effect of porSMNs by inhibiting the π–π stacking interactions of the photosensitizers, ablating of the tumors without relapse by taking advantage of photodynamic therapy.
Sophisticated porphyrin nanocages, which can be utilized as a functional platform to develop single molecular nanoparticles, were synthesized. The unique topological structure of the nanocages results in their excellent performance as cancer nanotheranostics, as demonstrated through applications in PET imaging and photodynamic therapy.
Magnetic–plasmonic hybrid nanoparticles (MPHNs) have attracted great interest in cancer theranostics. However, the relaxivity of the magnetic component is typically reduced by the plasmonic component ...in conventional core–shell structured MPHNs, due to the presence of a water‐impenetrable coating which severely restricts the proximity of protons to the magnetic portion. To circumvent this issue, yolk–shell structured MPHNs comprising a Fe3O4 core within a hollow cavity encircled by a porous Au outer shell are designed. As expected, the introduction of hollow cavity between the magnetic and plasmonic portions significantly prevents the decline in relaxivity of the Fe3O4 core caused by the Au layer. Moreover, in addition to conferring high near‐infrared absorption to plasmonic component, the hollow cavity and the pores in the outer shell can also provide a large storage space and release channels for anticancer drugs. Furthermore, the multicomponent nanoparticles (NPs) still have a compact size of less than 100 nm to ensure efficient tumor accumulation. Taken together, the yolk–shell Fe3O4@Au NPs can be regarded as an ideal magnetic–plasmonic theranostic platform for magnetic resonance/photoacoustic/positron emission tomography multimodal imaging and light‐activated chemothermal synergistic therapy.
Yolk–shell‐structured Fe3O4@Au nanoparticles are designed to circumvent the decline in the relaxivity of the magnetic component caused by the introduction of water‐impenetrable plasmonic components, which is unavoidable in traditional core–shell‐structured nanostructures. This feature, in conjunction with their compact size, near‐infrared absorption, and drug‐delivery capability, makes them harmoniously integrated magnetic–plasmonic theranostic nanoplatforms for multimodal imaging and light‐triggered chemothermal synergistic therapy.
Reactive oxygen species (ROS)-generating anticancer agents can act through two different mechanisms: (i) elevation of endogenous ROS production in mitochondria, or (ii) formation/delivery of ...exogenous ROS within cells. However, there is a lack of research on the development of ROS-generating nanosystems that combine endogenous and exogenous ROS to enhance oxidative stress-mediated cancer cell death.
A ROS-generating agent based on polymer-modified zinc peroxide nanoparticles (ZnO
NPs) was presented, which simultaneously delivered exogenous H
O
and Zn
capable of amplifying endogenous ROS production for synergistic cancer therapy.
After internalization into tumor cells, ZnO
NPs underwent decomposition in response to mild acidic pH, resulting in controlled release of H
O
and Zn
. Intriguingly, Zn
could increase the production of mitochondrial O
·
and H
O
by inhibiting the electron transport chain, and thus exerted anticancer effect in a synergistic manner with the exogenously released H
O
to promote cancer cell killing. Furthermore, ZnO
NPs were doped with manganese
cation exchange, making them an activatable magnetic resonance imaging contrast agent.
This study establishes a ZnO
-based theranostic nanoplatform which achieves enhanced oxidative damage to cancer cells by a two-pronged approach of combining endogenous and exogenous ROS.
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