Multifunctional Mesoporous Silica Nanoparticles with Thermal‐Responsive Gatekeeper for NIR Light‐Triggered Chemo/Photothermal‐Therapy

In this work, a matrix metalloproteinase (MMP)‐triggered tumor targeted mesoporous silica nanoparticle (MSN) is designed to realize near‐infrared (NIR) photothermal‐responsive drug release and combined chemo/photothermal tumor therapy. Indocyanine green (ICG) and doxorubicin (DOX) are both loaded in the MSN modified with thermal‐cleavable gatekeeper (Azo‐CD), which can be decapped by ICG‐generated hyperthermia under NIR illumination. A peptidic sequence containing a short PEG chain, matrix metalloproteinase (MMP) substrate (PLGVR) and tumor cell targeting motif (RGD) are further decorated on the MSN via a host–guest interaction. The PEG chain can protect the MSN during the circulation and be cleaved off in the tumor tissues with overexpressed MMP, and then the RGD motif is switched on to target tumor cells. After the tumor‐triggered targeting process, the NIR irradiation guided by ICG fluorescence can trigger cytosol drug release and realize combined chemo/photothermal therapy.     

Near‐Infrared Light Triggers Release of Paclitaxel from Biodegradable Microspheres: Photothermal Effect and Enhanced Antitumor Activity

Despite advances in controlled drug delivery, reliable methods for activatable, high‐resolution control of drug release are needed. The hypothesis that the photothermal effect mediated by a near‐infrared (NIR) laser and hollow gold nanospheres (HAuNSs) could modulate the release of anticancer agents is tested with biodegradable and biocompatible microspheres (1–15 µm) containing the antitumor drug paclitaxel (PTX) and HAuNSs (≈35 nm in diameter), which display surface plasmon absorbance in the NIR region. HAuNS‐containing microspheres exhibit a NIR‐induced thermal effect similar to that of plain HAuNSs. Rapid, repetitive PTX release from the PTX/HAuNS‐containing microspheres is observed upon irradiation with NIR light (808 nm), whereas PTX release is insignificant when the NIR light is switched off. The release of PTX from the microspheres is readily controlled by the output power of the NIR laser, duration of irradiation, treatment frequency, and concentration of HAuNSs embedded inside the microspheres. In vitro, cancer cells incubated with PTX/HAuNS‐loaded microspheres and irradiated with NIR light display significantly greater cytotoxic effects than cells incubated with the microspheres alone or cells irradiated with NIR light alone, owing to NIR‐light‐triggered drug release. Treatment of human U87 gliomas and MDA‐MB‐231 mammary tumor xenografts in nude mice with intratumoral injections of PTX/HAuNS‐loaded microspheres followed by NIR irradiation results in significant tumor‐growth delay compared to tumors treated with HAuNS‐loaded microspheres (no PTX) and NIR irradiation or with PTX/HAuNS‐loaded microspheres alone. The data support the feasibility of a therapeutic approach in which NIR light is used for simultaneous modulation of drug release and induction of photothermal cell killing.     

A Eutectic Mixture of Natural Fatty Acids Can Serve as the Gating Material for Near‐Infrared‐Triggered Drug Release

A smart release system responsive to near‐infrared (NIR) light is developed for intracellular drug delivery. The concept is demonstrated by coencapsulating doxorubicin (DOX) (an anticancer drug) and IR780 iodide (IR780) (an NIR‐absorbing dye) into nanoparticles made of a eutectic mixture of naturally occurring fatty acids. The eutectic mixture has a well‐defined melting point at 39 °C, and can be used as a biocompatible phase‐change material for NIR‐triggered drug release. The resultant nanoparticles exhibit prominent photothermal effect and quick drug release in response to NIR irradiation. Fluorescence microscopy analysis indicates that the DOX trapped in the nanoparticles can be efficiently released into the cytosol under NIR irradiation, resulting in enhanced anticancer activity. A new platform is thus offered for designing effective intracellular drug‐release systems, holding great promise for future cancer therapy.     

Ultrasound‐Propelled Nanoporous Gold Wire for Efficient Drug Loading and Release

Ultrasound (US)‐powered nanowire motors based on nanoporous gold segment are developed for increasing the drug loading capacity. The new highly porous nanomotors are characterized with a tunable pore size, high surface area, and high capacity for the drug payload. These nanowire motors are prepared by template membrane deposition of a silver‐gold alloy segment followed by dealloying the silver component. The drug doxorubicin (DOX) is loaded within the nanopores via electrostatic interactions with an anionic polymeric coating. The nanoporous gold structure also facilitates the near‐infrared (NIR) light controlled release of the drug through photothermal effects. Ultrasound‐driven transport of the loaded drug toward cancer cells followed by NIR‐light triggered release is illustrated. The incorporation of the nanoporous gold segment leads to a nearly 20‐fold increase in the active surface area compared to common gold nanowire motors. It is envisioned that such US‐powered nanomotors could provide a new approach to rapidly and efficiently deliver large therapeutic payloads in a target‐specific manner.     

Multifunctional RbxWO3 Nanorods for Simultaneous Combined Chemo‐photothermal Therapy and Photoacoustic/CT Imaging

Light‐triggered drug delivery based on near‐infrared (NIR)‐mediated photothermal nanocarriers has received tremendous attention for the construction of cooperative therapeutic systems in nanomedicine. Herein, a new paradigm of light‐responsive drug carrier that doubles as a photothermal agent is reported based on the NIR light‐absorber, Rb _x WO₃ (rubidium tungsten bronze, Rb‐TB) nanorods. With doxorubicin (DOX) payload, the DOX‐loaded Rb‐TB composite (Rb‐TB‐DOX) simultaneously provides a burst‐like drug release and intense heating effect upon 808‐nm NIR light exposure. MTT assays show the photothermally enhanced antitumor activity of Rb‐TB‐DOX to the MCF‐7 cancer cells. Most remarkably, Rb‐TB‐DOX combined with NIR irradiation also shows dramatically enhanced chemotherapeutic effect to DOX‐resistant MCF‐7 cells compared with free DOX, demonstrating the enhanced efficacy of combinational chemo‐photothermal therapy for potentially overcoming drug resistance in cancer chemotherapy. Furthermore, in vivo study of combined chemo‐photothermal therapy is also conducted and realized on pancreatic (Pance‐1) tumor‐bearing nude mice. Apart from its promise for cancer therapy, the as‐prepared Rb‐TB can also be employed as a new dual‐modal contrast agent for photoacoustic tomography and (PAT) X‐ray computed tomography (CT) imaging because of its high NIR optical absorption capability and strong X‐ray attenuation ability, respectively. The results presented in the current study suggest promise of the multifunctional Rb _x WO₃ nanorods for applications in cancer theranostics.     

Remote Light‐Responsive Nanocarriers for Controlled Drug Delivery: Advances and Perspectives

Engineering of smart photoactivated nanomaterials for targeted drug delivery systems (DDS) has recently attracted considerable research interest as light enables precise and accurate controlled release of drug molecules in specific diseased cells and/or tissues in a highly spatial and temporal manner. In general, the development of appropriate light‐triggered DDS relies on processes of photolysis, photoisomerization, photo‐cross‐linking/un‐cross‐linking, and photoreduction, which are normally sensitive to ultraviolet (UV) or visible (Vis) light irradiation. Considering the issues of poor tissue penetration and high phototoxicity of these high‐energy photons of UV/Vis light, recently nanocarriers have been developed based on light‐response to low‐energy photon irradiation, in particular for the light wavelengths located in the near infrared (NIR) range. NIR light‐triggered drug release systems are normally achieved by using two‐photon absorption and photon upconversion processes. Herein, recent advances of light‐responsive nanoplatforms for controlled drug release are reviewed, covering the mechanism of light responsive small molecules and polymers, UV and Vis light responsive nanocarriers, and NIR light responsive nanocarriers. NIR‐light triggered drug delivery by two‐photon excitation and upconversion luminescence strategies is also included. In addition, the challenges and future perspectives for the development of light triggered DDS are highlighted.     

Red‐Emitting Upconverting Nanoparticles for Photodynamic Therapy in Cancer Cells Under Near‐Infrared Excitation

Upconverting nanoparticles (UCNPs) have attracted considerable attention as potential photosensitizer carriers for photodynamic therapy (PDT) in deep tissues. In this work, a new and efficient NIR photosensitizing nanoplatform for PDT based on red‐emitting UCNPs is designed. The red emission band matches well with the efficient absorption bands of the widely used commercially available photosensitizers (Ps), benefiting the fluorescence resonance energy transfer (FRET) from UCNPs to the attached photosensitizers and thus efficiently activating them to generate cytotoxic singlet oxygen. Three commonly used photosensitizers, including chlorine e6 (Ce6), zinc phthalocyanine (ZnPc) and methylene blue (MB), are loaded onto the alpha‐cyclodextrin‐modified UCNPs to form Ps@UCNPs complexes that efficiently produce singlet oxygen to kill cancer cells under 980 nm near‐infrared excitation. Moreover, two different kinds of drugs are co‐loaded onto these nanoparticles: chemotherapy drug doxorubicin and PDT agent Ce6. The combinational therapy based on doxorubicin (DOX)‐induced chemotherapy and Ce6‐triggered PDT exhibits higher therapeutic efficacy relative to the individual means for cancer therapy in vitro.     

pH‐ and NIR Light‐Responsive Polymeric Prodrug Micelles for Hyperthermia‐Assisted Site‐Specific Chemotherapy to Reverse Drug Resistance in Cancer Treatment

Despite the exciting advances in cancer chemotherapy over past decades, drug resistance in cancer treatment remains one of the primary reasons for therapeutic failure. IR‐780 loaded pH‐responsive polymeric prodrug micelles with near infrared (NIR) photothermal effect are developed to circumvent the drug resistance in cancer treatment. The polymeric prodrug micelles are stable in physiological environment, while exhibit fast doxorubicin (DOX) release in acidic condition and significant temperature elevation under NIR laser irradiation. Phosphorylcholine‐based biomimetic micellar shell and acid‐sensitive drug conjugation endow them with prolonged circulation time and reduced premature drug release during circulation to conduct tumor site‐specific chemotherapy. The polymeric prodrug micelles combined with NIR laser irradiation could significantly enhance intracellular DOX accumulation and synergistically induce the cell apoptosis in DOX‐resistant MCF‐7/ADR cells. Meanwhile, the tumor site‐specific chemotherapy combined with hyperthermia effect induces significant inhibition of MCF‐7/ADR tumor growth in tumor‐bearing mice. These results demonstrate that the well‐designed IR‐780 loaded polymeric prodrug micelles for hyperthermia‐assisted site‐specific chemotherapy present an effective approach to reverse drug resistance.     

Free‐Blockage Mesoporous Anticancer Nanoparticles Based on ROS‐Responsive Wetting Behavior of Nanopores

To achieve an excellent delivery effect of drug, stimuli‐responsive nano “gate” with physical blockage units is usually constructed on the surface of the mesoporous silica nanocarriers (MSNs). In nature, the aquaporins in cell membrane can control the transport of water molecules by regulating the channel wettability, which is resulted from the conformational change of amino acids in the channel. Inspired by this phonomenon, herein a new concept of free‐blockage controlled release system is proposed, which is achieved by controlling the wettability of the internal surface of nanopores on MSNs. Such a new system is different from the physical‐blockage controlled release system, which bypasses the use of nano “gate” and overcomes the limitations of traditional physical blockage system. Moreover, further studies have shown that the system can selectively release the entrapped doxorubicin in human breast adenocarcinoma (MCF‐7) cells triggered by intracellular reactive oxygen species (ROS) but not in normalhuman umbilical vein endothelial cells (HUVECs) containing ROS with low levels. The wettability‐determined free‐blockage controlled release system is simple and effective, and it can also be triggered by intracellular biological stimuli, which provides a new approach for the future practical application of drug delivery and cancer therapy.     

Cyanine‐Anchored Silica Nanochannels for Light‐Driven Synergistic Thermo‐Chemotherapy

Smart nanoparticles are increasingly important in a variety of applications such as cancer therapy. However, it is still a major challenge to develop light‐responsive nanoparticles that can maximize the potency of synergistic thermo‐chemotherapy under light irradiation. Here, spatially confined cyanine‐anchored silica nanochannels loaded with chemotherapeutic doxorubicin (CS‐DOX‐NCs) for light‐driven synergistic cancer therapy are introduced. CS‐DOX‐NCs possess a J‐type aggregation conformation of cyanine dye within the nanochannels and encapsulate doxorubicin through the π–π interaction with cyanine dye. Under near‐infrared light irradiation, CS‐DOX‐NCs produce the enhanced photothermal conversion efficiency through the maximized nonradiative transition of J‐type Cypate aggregates, trigger the light‐driven drug release through the destabilization of temperature‐sensitive π–π interaction, and generate the effective intracellular translocation of doxorubicin from the lysosomes to cytoplasma through reactive oxygen species‐mediated lysosomal disruption, thereby causing the potent in vivo hyperthermia and intracellular trafficking of drug into cytoplasma at tumors. Moreover, CS‐DOX‐NCs possess good resistance to photobleaching and preferable tumor accumulation, facilitating severe photoinduced cell damage, and subsequent synergy between photothermal and chemotherapeutic therapy with tumor ablation. These findings provide new insights of light‐driven nanoparticles for synergistic cancer therapy.     

NIR‐Responsive Polycationic Gatekeeper‐Cloaked Hetero‐Nanoparticles for Multimodal Imaging‐Guided Triple‐Combination Therapy of Cancer

Responsive multifunctional organic/inorganic nanohybrids are promising for effective and precise imaging‐guided therapy of cancer. In this work, a near‐infrared (NIR)‐triggered multifunctional nanoplatform comprising Au nanorods (Au NRs), mesoporous silica, quantum dots (QDs), and two‐armed ethanolamine‐modified poly(glycidyl methacrylate) with cyclodextrin cores (denoted as CD‐PGEA) has been successfully fabricated for multimodal imaging‐guided triple‐combination treatment of cancer. A hierarchical hetero‐structure is first constructed via integration of Au NRs with QDs through a mesoporous silica intermediate layer. The X‐ray opacity and photoacoustic (PA) property of Au NRs are utilized for tomography (CT) and PA imaging, and the imaging sensitivity is further enhanced by the fluorescent QDs. The mesoporous feature of silica allows the loading of a typical antitumor drug, doxorubicin (DOX), which are sealed by the polycationic gatekeepers, low toxic hydroxyl‐rich CD‐PGEA/pDNA complexes, realizing the co‐delivery of drug and gene. The photothermal effect of Au NRs is utilized for photothermal therapy (PTT). More interestingly, such photothermal effect also induces a cascade of NIR‐triggered release of DOX through the facilitated detachment of CD‐PGEA gatekeepers for controlled chemotherapy. The resultant chemotherapy and gene therapy for glioma tumors are complementary for the efficiency of PTT. This work presents a novel responsive multifunctional imaging‐guided therapy platform, which combines fluorescent/PA/CT imaging and gene/chemo/photothermal therapy into one nanostructure.     

Two‐Dimensional Antimonene‐Based Photonic Nanomedicine for Cancer Theranostics

Antimonene (AM) is a recently described two‐dimensional (2D) elemental layered material. In this study, a novel photonic drug‐delivery platform based on 2D PEGylated AM nanosheets (NSs) is developed. The platform's multiple advantages include: i) excellent photothermal properties, ii) high drug‐loading capacity, iii) spatiotemporally controlled drug release triggered by near‐infrared (NIR) light and moderate acidic pH, iv) superior accumulation at tumor sites, v) deep tumor penetration by both extrinsic stimuli (i.e., NIR light) and intrinsic stimuli (i.e., pH), vi) excellent multimodal‐imaging properties, and vii) significant inhibition of tumor growth with no observable side effects and potential degradability, thus addressing several key limitations of cancer nanomedicines. The intracellular fate of the prepared NSs is also revealed for the first time, providing deep insights that improve cellular‐level understanding of the nano–bio interactions of AM‐based NSs and other emerging 2D nanomaterials. To the best of knowledge, this is the first report on 2D AM‐based photonic drug‐delivery platforms, possibly marking an exciting jumping‐off point for research into the application of 2D AM nanomaterials in cancer theranostics.     

Core–Satellite Polydopamine–Gadolinium‐Metallofullerene Nanotheranostics for Multimodal Imaging Guided Combination Cancer Therapy

Integration of magnetic resonance imaging (MRI) and other imaging modalities is promising to furnish complementary information for accurate cancer diagnosis and imaging‐guided therapy. However, most gadolinium (Gd)–chelator MR contrast agents are limited by their relatively low relaxivity and high risk of released‐Gd‐ions‐associated toxicity. Herein, a radionuclide‐⁶⁴Cu‐labeled doxorubicin‐loaded polydopamine (PDA)–gadolinium‐metallofullerene core–satellite nanotheranostic agent (denoted as CDPGM) is developed for MR/photoacoustic (PA)/positron emission tomography (PET) multimodal imaging‐guided combination cancer therapy. In this system, the near‐infrared (NIR)‐absorbing PDA acts as a platform for the assembly of different moieties; Gd₃N@C₈₀, a kind of gadolinium metallofullerene with three Gd ions in one carbon cage, acts as a satellite anchoring on the surface of PDA. The as‐prepared CDPGM NPs show good biocompatibility, strong NIR absorption, high relaxivity (r ₁ = 14.06 mM^?1 s^?1), low risk of release of Gd ions, and NIR‐triggered drug release. In vivo MR/PA/PET multimodal imaging confirms effective tumor accumulation of the CDPGM NPs. Moreover, upon NIR laser irradiation, the tumor is completely eliminated with combined chemo‐photothermal therapy. These results suggest that the CDPGM NPs hold great promise for cancer theranostics.     

Mesoporous‐Silica‐Coated Up‐Conversion Fluorescent Nanoparticles for Photodynamic Therapy

Near‐infrared (NIR)‐to‐visible up‐conversion fluorescent nanoparticles have potential to be used for photodynamic therapy (PDT) in deep tissue because NIR light can penetrate thick tissue due to weak absorption in the optical window. Here a uniform layer of mesoporous silica is coated onto NaYF₄ up‐converting nanocrystals, with a large surface area of ≈770 m² g^?1 and an average pore size of 2 nm. A photosensitizer, zinc phthalocyanine, is incorporated into the mesoporous silica. Upon excitation by a NIR laser, the nanocrystals convert NIR light to visible light, which further activates the photosensitizer to release reactive singlet oxygen to kill cancer cells. The photosensitizer encapsulated in mesoporous silica is protected from degradation in the harsh biological environment. It is demonstrated that the photosensitizers loaded into the porous silica shell of the nanoparticles are not released out of the silica while they continuously produce singlet oxygen upon excitation by a NIR laser. The nanoparticles are reusable as the photosensitizers encapsulated in the silica are removed by soaking in ethanol.     

Cancer Cell Membrane Camouflaged Semi‐Yolk@Spiky‐Shell Nanomotor for Enhanced Cell Adhesion and Synergistic Therapy

Cell adhesion of nanosystems is significant for efficient cellular uptake and drug delivery in cancer therapy. Herein, a near‐infrared (NIR) light‐driven biomimetic nanomotor is reported to achieve the improved cell adhesion and cellular uptake for synergistic photothermal and chemotherapy of breast cancer. The nanomotor is composed of carbon@silica (C@SiO₂) with semi‐yolk@spiky‐shell structure, loaded with the anticancer drug doxorubicin (DOX) and camouflaged with MCF‐7 breast cancer cell membrane (i.e., mC@SiO₂@DOX). Such biomimetic mC@SiO₂@DOX nanomotors display efficient self‐thermophoretic propulsion due to a thermal gradient generated by asymmetrically spatial distribution. Moreover, the MCF‐7 cancer cell membrane coating can remarkably reduce the bioadhesion of nanomotors in biological medium and exhibit highly specific self‐recognition of the source cell line. The combination of effective propulsion and homologous targeting dramatically improves cell adhesion and the resultant cellular uptake efficiency in vitro from 26.2% to 67.5%. Therefore, the biomimetic mC@SiO₂@DOX displays excellent synergistic photothermal and chemotherapy with over 91% MCF‐7 cell growth inhibition rate. Such smart design of the fuel‐free, NIR light‐powered biomimetic nanomotor may pave the way for the application of self‐propelled nanomotors in biomedicine.     

Combined Near Infrared Photothermal Therapy and Chemotherapy Using Gold Nanoshells Coated Liposomes to Enhance Antitumor Effect

Novel antitumor system based on the targeting photothermal and pH‐responsive nanocarriers, gold nanoshells coated oleanolic acid liposomes mediating by chitosan (GNOLs), is designed and synthesized for the first time. The GNOLs present spherical and uniform size (172.03 nm) with zeta potential (20.7 ± 0.4 mV), which are more easily accumulated in tumor. Meanwhile, the GNOLs exhibit a slow and controlled release of oleanolic acid at pH 7.4, as well as a rapid release at pH 5.5, which is beneficial for tumor‐targeting drug release. Under near infrared (NIR) irradiation, hyperthermia can be generated by activated gold nanoshells to perform photothermal therapy effect, which triggers drug release from the carriers by activating the gel to liquid crystalline phase transition of the liposomes. Moreover, the NIR assisting drug release can be easily and selectively activated locally due to the spatially and real‐timely controllable property of light. The experimental results also verify that the GNOLs with NIR irradiation achieve more ideal antitumor effects than other oleanolic acid formulations in vitro and in vivo. Hence, the drug delivery system exhibits a great potential in chemo‐photothermal antitumor therapy.     

Self‐Amplified Drug Delivery with Light‐Inducible Nanocargoes to Enhance Cancer Immunotherapy

Chemoimmunotherapy by systemic administration of individual regimens suffers from inconsistent pharmacokinetics profiles, low tumor specificity, and severe side effects. Despite promising nanoparticle‐based codelivery approaches in therapeutics, the pathophysiological barriers of solid tumors are a hurdle for tumor accumulation and deep penetration of the drug‐loaded nanoparticles. A light‐inducible nanocargo (LINC) for immunotherapy is reported. LINC is composed of a reduction‐responsive heterodimer of photosensitizer pheophorbide A (PPa) and indoleamine 2,3‐dioxygenase 1 (IDO‐1) inhibitor, i.e., NLG919, and a light‐activatable prodrug of oxaliplatin (OXA). LINC administrated through intravenous injection is passively accumulated at the tumor site to generate near‐infrared (NIR) fluorescence signal. Under fluorescence imaging guidance, the first‐wave of NIR laser irradiation induce reactive oxygen species (ROS) generation, trigger cleavage of the polyethylene glycol (PEG) corona, and thus promote tumor retention and deep penetration of LINC. When exposed to the second‐wave NIR laser illumination, LINC efficiently elicits the immune response and promotes intratumoral infiltration of cytotoxic T lymphocytes (CTLs). Furthermore, NLG919 delivered by LINC reverses the immunosuppressive tumor microenvironment by suppressing IDO‐1 activity. Chemoimmunotherapy with LINC inhibit the tumor growth, lung metastasis, and tumor recurrence. The light‐inducible self‐amplification strategy for improved drug delivery and immunotherapy shows potential.     

A Rationally Designed Semiconducting Polymer Brush for NIR‐II Imaging‐Guided Light‐Triggered Remote Control of CRISPR/Cas9 Genome Editing

The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR‐associated protein 9 (Cas9) genome‐editing system has shown great potential in biomedical applications. Although physical approaches, viruses, and some nonviral vectors have been employed for CRISPR/Cas9 delivery and induce some promising genome‐editing efficacy, precise genome editing remains challenging and has not been reported yet. Herein, second near‐infrared window (NIR‐II) imaging‐guided NIR‐light‐triggered remote control of the CRISPR/Cas9 genome‐editing strategy is reported based on a rationally designed semiconducting polymer brush (SPPF). SPPF can not only be a vector to deliver CRISPR/Cas9 cassettes but also controls the endolysosomal escape and payloads release through photothermal conversion under laser irradiation. Upon laser exposure, the nanocomplex of SPPF and CRISPR/Cas9 cassettes induces effective site‐specific precise genome editing both in vitro and in vivo with minimal toxicity. Besides, NIR‐II imaging based on SPPF can also be applied to monitor the in vivo distribution of the genome‐editing system and guide laser irradiation in real time. Thus, this study offers a typical paradigm for NIR‐II imaging‐guided NIR‐light‐triggered remote control of the CRISPR/Cas9 system for precise genome editing. This strategy may open an avenue for CRISPR/Cas9 genome‐editing‐based precise gene therapy in the near future.     

Let There be Light: Polymeric Micelles with Upper Critical Solution Temperature as Light‐Triggered Heat Nanogenerators for Combating Drug‐Resistant Cancer

Complete drug release and efficient drug retention are two critical factors in reversing drug resistance in cancer therapy. In this regard, polymeric micelles with an upper critical solution temperature (UCST) are designed as a new exploration to reverse drug resistance. The amphiphilic UCST‐type block copolymers are used to encapsulate photothermal agent IR780 and doxorubicin (DOX) simultaneously. The integrated UCST‐type drug nanocarriers show light‐triggered multiple synergistic effects to reverse drug resistance and are expected to kill three birds with one stone: First, owing to the photothermal effect of IR780, the nanocarriers will be dissociated upon exposure to laser irradiation, leading to complete drug release. Second, the photothermal effect‐induced hyperthermia is expected to avoid the efflux of DOX and realize efficient drug retention. Last but not least, photothermal ablation of cancer cells can be achieved after laser irradiation. Therefore, the UCST‐type drug nanocarriers provide a new strategy in reversing drug resistance in cancer therapy.     

Dual‐Stimuli Responsive Nanotheranostics for Multimodal Imaging Guided Trimodal Synergistic Therapy

Multimodal imaging guided synergistic therapy promises more accurate diagnosis than any single imaging modality, and higher therapeutic efficiency than any single one or their simple “mechanical” combination. Herein, we report a dual‐stimuli responsive nanotheranostic based on a hierarchical nanoplatform, composed of mesoporous silica‐coated gold nanorods (GNR@SiO2), Indocyanine Green (ICG), and 5‐fluorouracil (5‐FU), for in vivo multimodal imaging guided synergistic therapy. The 5‐FU loaded ICG‐conjugated silica‐coated gold nanorods (GNR@SiO2‐5‐FU‐ICG) was able to response specifically to the two stimuli of pH change and near‐infrared (NIR) light irradiation. Both the NIR light irradiation and acidic environment accelerated the 5‐FU release. Meanwhile, the heat generation and singlet oxygen production can be induced by GNR@SiO2‐5‐FU‐ICG upon light irradiation. Most intriguingly, the nanoplatform also promises multimodal imaging such as two‐photon luminescence, fluorescence, photoacoustic, photothermal imaging, as well as trimodal synergistic therapy such as photothermal therapy (PTT), photodynamic therapy (PDT), and chemotherapy. The cancer theranostic capability of GNR@SiO2‐5‐FU‐ICG was evaluated both in vitro and in vivo. The trimodal synergistic therapy with the guidance of multimodal imaging exhibited remarkably enhanced treatment efficacy. This concept of a hierarchical nanoplatform integrates multiple diagnostic/therapeutic modalities into one platform, which can potentially be applied as personalized nanomedicine with drug delivery, diagnosis, and treatment.