In order to selectively target malignant cells and eliminate severe side effects of conventional chemotherapy, biocompatible and redox-responsive hollow nanocontainers with tumor specificity were fabricated. The mechanized nanocontainers were achieved by anchoring mechanically interlocked molecules, i.e., [2]rotaxanes, onto the orifices of hollow mesoporous silica nanoparticles via disulfide bonds as intermediate linkers for intracellular glutathione-triggered drug release. The [2]rotaxane employed was mainly composed of U.S. Food and Drug Administration approved tetraethylene glycol chains, α-cyclodextrin, and folic acid. In this study, folate groups on the mechanized hollow nanocontainers act as both the tumor-targeting agents and stoppers of the [2]rotaxanes. Detailed investigations showed that anticancer drug doxorubicin loaded mechanized nanocontainers could selectively induce the apoptosis and death of tumor cells. The drug-loaded nanocontainers enhanced the targeting capability to tumor tissues in vitro and inhibited the tumor growth with minimal side effects in vivo. The present controlled and targeted drug delivery system paves the way for developing the next generation of nanotherapeutics toward efficient cancer treatment.

In treatment of hypoxic tumors, oxygen‐dependent photodynamic therapy (PDT) is considerably limited. Herein, a new bimetallic and biphasic Rh‐based core–shell nanosystem (Au@Rh‐ICG‐CM) is developed to address tumor hypoxia while achieving high PDT efficacy. Such porous Au@Rh core–shell nanostructures are expected to exhibit catalase‐like activity to efficiently catalyze oxygen generation from endogenous hydrogen peroxide in tumors. Coating Au@Rh nanostructures with tumor cell membrane (CM) enables tumor targeting via homologous binding. As a result of the large pores of Rh shells and the trapping ability of CM, the photosensitizer indocyanine green (ICG) is successfully loaded and retained in the cavity of Au@Rh‐CM. Au@Rh‐ICG‐CM shows good biocompatibility, high tumor accumulation, and superior fluorescence and photoacoustic imaging properties. Both in vitro and in vivo results demonstrate that Au@Rh‐ICG‐CM is able to effectively convert endogenous hydrogen peroxide into oxygen and then elevate the production of tumor‐toxic singlet oxygen to significantly enhance PDT. As noted, the mild photothermal effect of Au@Rh‐ICG‐CM also improves PDT efficacy. By integrating the superiorities of hypoxia regulation function, tumor accumulation capacity, bimodal imaging, and moderate photothermal effect into a single nanosystem, Au@Rh‐ICG‐CM can readily serve as a promising nanoplatform for enhanced cancer PDT.

A novel redox responsive controlled drug release system based on magnetic nanoparticles for efficient intracellular anticancer drug delivery is fabricated. Disulfide bonds are employed as intermediate linkers to immobilize PEI/β-CD molecules as nanoreservoirs for drug loading onto magnetic nanoparticles. The endocytotic pathway and endosomal escape of the smart controlled drug release system is proposed.

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A nanoreservoir for efficient intracellular anticancer drug delivery based on mesoporous silica nanoparticles end-capped with lactobionic acid-grafted bovine serum albumin is fabricated. It demonstrates great potential for both cell-specific endocytosis and intracellular pH-responsive controlled release of drugs. A possible endocytosis pathway/mechanism of the smart controlled drug release system is proposed.

Gold‐based nanostructures with tunable wavelength of localized surface plasmon resonance (LSPR) in the second near‐infrared (NIR‐II) biowindow receive increasing attention in phototheranostics. In view of limited progress on NIR‐II gold nanostructures, a particular liposome template‐guided route is explored to synthesize novel gold nanoframeworks (AuNFs) with large mesopores (≈40 nm) for multimodal imaging along with therapeutic robustness. The synthesized AuNFs exhibit strong absorbance in NIR‐II region, affording their capacity of NIR‐II photothermal therapy (PTT) and photoacoustic (PA) imaging for deep tumors. Functionalization of AuNFs with hyaluronic acid (HA) endows the targeting capacity for CD44‐overexpressed tumor cells while gatekeeping doxorubicin (DOX) loaded into mesopores. Conjugation of Raman reporter 4‐aminothiophenol (4‐ATP) onto AuNFs yields a surface‐enhanced Raman scattering (SERS) fingerprint for Raman spectroscopy/imaging. In vivo evaluation of HA‐4‐ATP‐AuNFs‐DOX on tumor‐bearing xenografts demonstrates its high efficacy in eradication of solid tumors in NIR‐II under PA–Raman dual image‐guided photo‐chemotherapy. Thus, current AuNFs offer versatile capabilities for phototheranostics.

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This study reports a biocompatible controlled drug release system based on mesoporous silica nanoparticles (MSNs) for tumor microenvironment responsive drug delivery. It was fabricated by grafting phenylboronic acid conjugated human serum albumin (PBA-HSA) onto the surfaces of MSNs as a sealing agent, via an intermediate linker of a functional polypeptide, which was composed of two functional units: the polycation cell penetrating peptide (CPP) polyarginine, and matrix metalloproteinase 2 (MMP-2) substrate peptide. A series of characterizations confirmed that the system had been successfully constructed. In vitro tests proved that the anticancer drug loading system could efficiently induce cell apoptosis in vitro. More importantly, the in vivo tumor experiments confirmed that the anticancer loading system could efficiently inhibit tumor growth with minimal side effects.