Cancer Therapeutic Efficiency Research Articles

Artificial intelligence in gastrointestinal cancers: diagnostic, prognostic, and surgical strategies.

GI (Gastrointestinal) malignancies are one of the most common and lethal cancers globally. The dawn of precision medicine and developing technologies have reduced the mortality rates for GI malignancies, underscoring the main role of early detection methods for survival rate improvement. Artificial intelligence (AI) is a new technology that may improve GI cancer screening, treatment, and therapeutic efficiency for better patient care. AI could accelerate the development of targeted therapies by analyzing considerable data from the genome and identifying biomarkers connected with GI tumors. This opens up new avenues toward more tailored and personalized approaches, raising efficacy while reducing undesired side effects. For instance, AI may improve treatment outcomes by accurately predicting patient responses to therapeutic regimens, helping oncologists choose the most effective treatment options. This review will outline the transformative potential of AI in GI oncology by emphasizing the incorporation of AI-based technologies to enhance patient care.

Apoptosis and Paraptosis Induced by Disulfiram-Loaded Ca2+/Cu2+ Dual-Ions Nano Trap for Breast Cancer Treatment.

Regarded as one of the hallmarks of tumorigenesis and tumor progression, the evasion of apoptotic cell death would also account for treatment resistance or failure during cancer therapy. In this study, a Ca2+/Cu2+ dual-ion "nano trap" to effectively avoid cell apoptosis evasion by synchronously inducing paraptosis together with apoptosis was successfully designed and fabricated for breast cancer treatment. In brief, disulfiram (DSF)-loaded amorphous calcium carbonate nanoparticles (NPs) were fabricated via a gas diffusion method. Further on, the Cu2+-tannic acid metal phenolic network was embedded onto the NPs surface by self-assembling, followed by mDSPE-PEG/lipid capping to form the DSF-loaded Ca2+/Cu2+ dual-ions "nano trap". The as-prepared nanotrap would undergo acid-triggered biodegradation upon being endocytosed by tumor cells within the lysosome for Ca2+, Cu2+, and DSF releasing simultaneously. The released Ca2+ could cause mitochondrial calcium overload and lead to hydrogen peroxide (H2O2) overexpression. Meanwhile, Ca2+/reactive oxygen species-associated mitochondrial dysfunction would lead to paraptosis cell death. Most importantly, cell paraptosis could be further induced and strengthened by the toxic dithiocarbamate (DTC)-copper complexes formed by the Cu2+ combined with the DTC, the metabolic products of DSF. Additionally, the released Cu2+ will be reduced by intracellular glutathione to generate Cu+, which can catalyze the H2O2 to produce a toxic hydroxyl radical by a Cu+-mediated Fenton-like reaction for inducing cell apoptosis. Both in vitro cellular assays and in vivo antitumor evaluations confirmed the cancer therapeutic efficiency by the dual ion nano trap. This study can broaden the cognition scope of dual-ion-mediated paraptosis together with apoptosis via a multifunctional nanoplatform.

A convergent fabrication of programmed pH/reduction-responsive nanoparticles for efficient dual anticancer drugs delivery for ovarian cancer treatment

A nanoparticle-based drug delivery technology could develop combination cancer therapy more effectively. However, because of inadequate drug delivery into tumor cells, the cancer therapeutic efficiency of nanomedicines is diminished. PEGylated poly(α-lipoic acid) copolymers with (mPEG-PLA) were fabricated and used as pH/reductive responsive nanovesicles to administer Gefitinib (GFT) and doxorubicin (DOX) for the treatment of ovarian cancer. The amphiphilic polymers mPEG-PLA may be efficiently incorporated on DOX and GFT to fabricate DOX and GFT coloaded nanoparticles (DOX@GFT-NPs) and self-assembled into an aqueous solution. The DOX@GFT-NPs released more DOX and GFT after being prepared to respond to pH and reduction stimuli. The outcomes of confocal laser scanning microscopy and flow cytometry findings, the SKOV3 ovarian cancer cells quickly fascinated the dual drugs-coloaded nanoparticles and drugs released intracellularly accumulated. DOX@GFT-NPs triggered cell death and demonstrated synergistic therapeutic benefits in SKOV3 cells. Results showed that the nanoparticles efficiently trigger apoptosis in SKOV3 ovarian cancer cells using morphological staining (acridine orange/ethidium bromide (AO/EB) and HOECHST 33342 nuclear staining). These outcomes show that using pH and reduction stimuli on mPEG-PLA copolymer to treat ovarian cancer is a promising approach.

Low-dose X-ray radiodynamic therapy solely based on gold nanoclusters for efficient treatment of deep hypoxic solid tumors combined with enhanced antitumor immune response.

Background: Radiodynamic therapy (RDT) is an emerging novel anti-cancer treatment based on the generation of cytotoxic reactive oxygen species (ROS) at the lesion site following the interaction between low-dose X-ray and a photosensitizer (PS) drug. For a classical RDT, scintillator nanomaterials loaded with traditional PSs are generally involved to generate singlet oxygen (1O2). However, this scintillator-mediated strategy generally suffers from insufficient energy transfer efficiency and the hypoxic tumor microenvironment, and finally severely impedes the efficacy of RDT. Methods: Gold nanoclusters were irradiated by low dose of X-ray (called RDT) to investigate the production of ROS, killing efficiency of cell level and living body level, antitumor immune mechanism and biosafety. Results: A novel dihydrolipoic acid coated gold nanoclusters (AuNC@DHLA) RDT, without additional scintillator or photosensitizer assisted, has been developed. In contrast to scintillator-mediated strategy, AuNC@DHLA can directly absorb the X-ray and exhibit excellent radiodynamic performance. More importantly, the radiodynamic mechanism of AuNC@DHLA involves electron-transfer mode resulting in O2 -• and HO•, and excess ROS has been generated even under hypoxic conditions. Highly efficient in vivo treatment of solid tumors had been achieved via only single drug administration and low-dose X-ray radiation. Interestingly, enhanced antitumor immune response was involved, which could be effective against tumor recurrence or metastasis. Negligible systemic toxicity was also observed as a consequence of the ultra-small size of AuNC@DHLA and rapid clearance from body after effective treatment. Conclusions: Highly efficient in vivo treatment of solid tumors had been achieved, enhanced antitumor immune response and negligible systemic toxicity were observed. Our developed strategy will further promote the cancer therapeutic efficiency under low dose X-ray radiation and hypoxic conditions, and bring hope for clinical cancer treatment.

Carrier-Free ATP-Activated Nanoparticles for Combined Photodynamic Therapy and Chemotherapy under Near-Infrared Light.

The combination of photodynamic therapy (PDT) and chemotherapy (chemo-photodynamic therapy) for enhancing cancer therapeutic efficiency has attracted tremendous attention in the recent years. However, limitations, such as low local concentration, non-suitable treatment light source, and uncontrollable release of therapeutic agents, result in reduced combined treatment efficacy. This study considered adenosine triphosphate (ATP), which is highly upregulated in tumor cells, as a biomarker and developed ingenious ATP-activated nanoparticles (CDNPs) that are directly self-assembled from near-infrared photosensitizer (Cy-I) and amphiphilic Cd(II) complex (DPA-Cd). After selective entry into tumor cells, the positively charged CDNPs would escape from lysosomes and be disintegrated by the high ATP concentration in the cytoplasm. The released Cy-I is capable of producing single oxygen (1 O2 ) for PDT with 808nm irradiation and DPA-Cd can concurrently function for chemotherapy. Irradiation with 808nm light can lead to tumor ablation in tumor-bearing mice after intravenous injection of CDNPs. This carrier-free nanoparticle offers a new platform for chemo-photodynamic therapy.

Rational design of pH-activated upconversion luminescent nanoprobes for bioimaging of tumor acidic microenvironment and the enhancement of photothermal therapy

The development of effective and safe tumor photothermal therapeutic strategies has attracted considerable attention. Herein, we synthesized tumor microenvironment (TME)-activatable self-assembling organic nanotheranostics (NRhD-PEG-X NPs (X = 1, 2, 3, and 4)) for precise tumor targeting and upconversion image-guided photothermal therapy (PTT). The amphiphilic polymer NRhD-PEG-X consisted of upconversion luminescent probes (NRhD) modified with polyethylene glycol (PEG) of various lengths. The continuous external irradiation-free photothermal NRhD-PEG-4 NPs with pKa 6.70 displayed high sensitivity and selectivity to protons, resulting in the turn-on upconversion luminescence and enhanced photothermal properties in the acidic TME without asynchronous therapy and side effects. This nanotheranostic offers acidic activatability, tumor targetability, and PTT enhancement, thus allowing autofluorescence-free upconversion luminescent imaging-guided precision PTT. Our strategy affords a paradigm to develop activatable theranostic nanoplatforms for precision medicine. Statement of significanceAs a hyperthermia-based treatment, activatable photothermal therapy (PTT) is highly significant in tumor treatment. Herein, we develop acidic tumor microenvironment-activatable nanotheranostics for upconversion luminescent imaging-guided diagnosis and precision tumor-targeted PTT. PEGylation of upconversion dyes not only could self-assemble to yield organic nanoparticles in water, but it could also significantly improve biocompatibility, stability, and circulation time and tune significantly the pKa value of nanoparticles. In an acidic tumor microenvironment, NRhD-PEG-4 NPs with pKa 6.70 show high sensitivity to release NRhDH+-PEG-4 NPs, which exhibit good upconversion luminescence and enhanced photothermal effect. Therefore, upconversion luminescence imaging-guided precision PTT has high potential to enhance cancer diagnostic and therapeutic efficiency.

Recent Progress in Second Near-Infrared (NIR-II) Fluorescence Imaging in Cancer.

Cancer continues to be one of the leading causes of death worldwide, and its incidence is on the rise. Although cancer diagnosis and therapy have advanced significantly in recent decades, it is still a challenge to achieve the accurate identification and localization of cancer and to complete tumor elimination with a maximum preservation of normal tissue. Recently, second near-infrared region (NIR-II, 1000–1700 nm) fluorescence has shown great application potential in cancer theranostics due to its inherent advantages, such as great penetration capacity, minimal tissue absorption and scattering, and low autofluorescence. With the development of fluorescence imaging systems and fluorescent probes, tumor detection, margin definition, and individualized therapy can be achieved quickly, enabling an increasingly accurate diagnosis and treatment of cancer. Herein, this review introduces the role of NIR-II fluorescence imaging in cancer diagnosis and summarizes the representative applications of NIR-II image-guided treatment in cancer therapy. Ultimately, we discuss the present challenges and future perspectives on fluorescence imaging in the field of cancer theranostics and put forward our opinions on how to improve the accuracy and efficiency of cancer diagnosis and therapeutics.

Library Screening to Identify Highly-Effective Autophagy Inhibitors for Improving Photothermal Cancer Therapy.

The small molecular inhibitor-associated downregulation of autophagy can remarkably enhance the efficiency of photothermal cancer therapy. To identify a more effective autophagy inhibitor, we screened a library of 20 compounds and found chloroquine, hydroxychloroquine, dauricine, and daurisoline were more efficient than the others to improve the photothermal killing of cancer cells. Interestingly, the four agents all disturb the autophagosome formation and fusion process, indicating it is a promising target to enhance cancer therapeutic efficiency. Among the four agents, daurisoline was identified to be the most efficient one. It reduced the viability of cancer cells treated by low-energy photothermal therapy from 86.27% to 32.92%. Finally, the combination treatment mediated by nanodrugs loaded with daurisoline and indocyanine green was more efficient than the individual modalities, resulting in complete inhibition of tumor growth. The study gives new inspiration to autophagy modulation-associated photothermal therapy and other therapeutic modalities for cancer treatment.

Enhanced cancer therapeutic efficiency of NO combined with siRNA by caspase-3 responsive polymers

The combination of nitric oxide (NO) and siRNA is highly desirable for cancer therapy. Here, the furoxans-grafted PEI polymer (FDP) with caspase-3 responsive cleavable DEVD linker was synthesized, and used to bind siRNAs via electrostatic interaction and self-assembled into FDP/siRNA nanoplexes by hydrophobic force. After cellular uptake and lysosomal escape, the FDP/siRNA nanoplexes could achieve GSH-triggered NO release, and then increase the activity of caspase-3. The activated caspase-3 could specifically cleave the DEVD peptide sequence and enhance cell apoptosis. With the cleavage of DEVD peptide sequence, the disassembly of FDP/siRNA nanoplexes was further promoted, thereby resulting in increased siRNAs of ~40% were released at 48 h compared with the caspase-3 non-responsive FDnP/siRNA nanoplexes. By this way, cell apoptosis promotion and cell proliferation inhibition was achieved by siRNA-based downregulation of EGFR protein and the upregulated activity of caspase-3, followed by the enhanced cascade release of NO from FDP/siRNA nanoplexes. Furthermore, in vivo results demonstrated the improved anti-cancer efficiency of FDP/siEGFR nanoplexes without any detectable side effects. Therefore, it is believed that the caspase-3 responsive cleavable furoxans-grafted PEI polymers could provide a potential and efficient enhancement for cancer therapeutic efficiency by the co-delivery of nitric oxide and siRNA.

Self-Assembled Hybrid Nanogel as a Multifunctional Theranostic Probe for Enzyme-Regulated Ultrasound Imaging and Tumor Therapy.

Multifunctional theranostic nanoprobes integrated with stimuli-responsive imaging and therapeutic capabilities have shown great potential to enhance the early cancer diagnostic efficacy and therapeutic efficiency. Elevated levels of lactate and hydrogen peroxide have been considered as the characteristic feature of the tumor microenvironment and can thus be exploited for developing promising theranostic strategies. We demonstrate here that the biocompatible and responsive enzyme-based nanogel probe has been designed as a promising theranostic tool to target high lactate and hydrogen peroxide for ultrasound imaging (US) and cancer treatment. We encapsulate the dual enzyme lactate oxidase (LOD) and catalase (CAT) into the self-assembled nanogels to fabricate responsive nanoprobe LOD/CAT-loaded nanogels (LCNGs). The nanoprobes can respond to the lactate and H2O2 rich tumor microenvironment to generate abundant oxygen, which further accumulates into microbubbles for enhanced US imaging. Besides, LCNGs@DOX has been further created by integrating the nanoprobes with doxorubicin (DOX) for cancer therapy. Both in vitro and in vivo results demonstrate enhanced US imaging and effective cell proliferation inhibition of LCNGs@DOX, allowing the preparation of safe and efficient theranostic nanoprobes capable of responsive US imaging and treating tumors.

Reduction-Responsive Chemo-Capsule-Based Prodrug Nanogel for Synergistic Treatment of Tumor Chemotherapy.

Chemotherapy is currently the most universal therapeutics to tumor treatment; however, limited curative effect and undesirable drug resistance effect are the two major clinical bottlenecks. Herein, we develop a two-in-one cross-linking strategy to prepare a stimuli-responsive prodrug nanogel by virtue of delivering a combination of chemotherapeutic drugs of 10-hydroxy camptothecin and doxorubicin for ameliorating the deficiencies of chemotherapy and amplifying the cancer therapeutic efficiency. The obtained prodrug nanogel has both high drug loading capacity and suitable nanoscale size, which are beneficial to the cell uptake and tumor penetration. Moreover, the chemotherapeutic drugs are released from the prodrug nanogel in response to the reductive tumor microenvironment, enhancing tumor growth inhibition in vitro and in vivo by the synergistic DNA damage. Based on these results, the unique prodrug nanogel would be a promising candidate for satisfactory tumor treatment-based chemotherapy by a simple but efficient strategy.

Morphological and constituent viral-mimicking self-assembled nanoparticles promote cellular uptake and improve cancer therapeutic efficiency in vivo

The delivery of nanomaterials or therapeutics into cells takes a decisive role for their applications in nanomedicine. Nature's creations such as viruses provide valued inspiration for design of nano-architectures in cellular delivery. We report herein the fabrication of biodegradable and biocompatible nanoparticles (NPs) with viral-mimicking morphology and constituents as a nanoplatform, which has rarely been reported to the best of our knowledge, for promoting cellular uptake and achieving high therapeutic efficiency in vivo. The chitosan-porphyrin-based NPs were endowed with a viral-imitating morphology through a novel pH-responsive decomposition-induced self-assembly method. By successive conjugation of Tat peptides and modification of lipids, morphological and constituent viral-mimicking NPs were obtained. Compared with the counterpart of non-viral-mimicking NPs, the viral-mimicking NPs showed prominent superiority in enhancing cell internalization (10 times higher). Loading of near-infrared photosensitizer– indocyanine green into these NPs demonstrated the striking capability of the viral-mimicking nanoparticles in therapeautic delivery and photothermal anti-tumor effect in vitro and in vivo. This concept and strategy provides an enlightening methodology on the design and fabrication of therapeutic delivery systems, which is significant for nanobiotechnology.

Tetrahedral DNA nanostructures as drug delivery and bioimaging platforms in cancer therapy.

Structural DNA nanotechnology enables DNA to be used as nanomaterials for novel nanostructure construction with unprecedented functionalities. Artificial DNA nanostructures can be designed and generated with precisely controlled features, resulting in its utility in bionanotechnological and biomedical applications. A tetrahedral DNA nanostructure (TDN), the most popular DNA nanostructure, with high stability and simple synthesis procedure, is a promising candidate as nanocarriers in drug delivery and bioimaging platforms, particularly in precision medicine as well as diagnosis for cancer therapy. Recent evidence collectively indicated that TDN successfully enhanced cancer therapeutic efficiency both in vitro and in vivo. Here, we summarize the development of TDN and highlight various aspects of TDN applications in cancer therapy based on previous reports, including anticancer drug loading, photodynamic therapy, therapeutic oligonucleotides, bioimaging platforms, and other molecules and discuss a perspective in opportunities and challenges for future TDN‐based nanomedicine.

PH-Responsive hyperbranched polypeptides based on Schiff bases as drug carriers for reducing toxicity of chemotherapy.

Polymeric micelles have great potential in drug delivery systems because of their multifunctional adjustability, excellent stability, and biocompatibility. To further increase the drug loading efficiency and controlled release ability, a pH-responsive hyperbranched copolymer methoxy poly(ethylene glycol)-b-polyethyleneimine-poly(Nε-Cbz-l-lysine) (MPEG-PEI-PBLL) was synthesized successfully. MPEG-PEI-NH2 was synthesized to initiate the ring-opening polymerization of benzyloxycarbonyl substituted lysine N-carboxyanhydride (Z-lys NCA). The introduction of Schiff bases in the polymer make it possible to respond to the variation of pH values, which cleaved at pH 5.0 while stable at pH 7.4. As the polymer was amphiphilic, MPEG-PEI-PBLL could self-assemble into micelles. Owing to the introduction of PEI, which make the copolymer hyperbranched, the pH-responsive micelles could efficiently encapsulate theranostic agents, such as doxorubicin (DOX) for chemotherapy and NIRF dye DiD for in vivo near-infrared (NIR) imaging. The drug delivery system prolonged the drug circulation time in blood and allowed the drug accumulate effectively at the tumor site. Following the guidance, the DOX was applied in chemotherapy to achieve cancer therapeutic efficiency. All the results demonstrate that the polymer micelles have great potential for cancer theranostics.

Multifunctional Albumin-Based Delivery System Generated by Programmed Assembly for Tumor-Targeted Multimodal Therapy and Imaging.

To enhance the treatment efficiency in tumor therapy, we developed a tumor-targeting protein-based delivery system, DOX&ICG@BSA-KALA/Apt, to efficiently integrate multimodal therapy with tumor imaging and realize synchronous photodynamic therapy/photothermal therapy/chemotherapy. In the delivery system, a chemotherapeutic drug (doxorubicin, DOX) and an optotheranostic agent (indocyanine green, ICG) were co-loaded in bovine serum albumin (BSA) via a hydrophobic-interaction-induced self-assembly to form stable DOX&ICG@BSA nanoparticles. After the decoration of a surface layer composed of a tumor-targeting aptamer (AS1411) and a cell-penetrating peptide (KALA), the obtained DOX&ICG@BSA-KALA/Apt nanoparticles exhibit a significantly improved multimodal cancer therapeutic efficiency due to the enhanced cancer cellular uptake mediated by AS1411 and KALA. In vitro and in vivo studies show that the multimodal theranostic system can efficiently inhibit tumor growth. In addition, the near-infrared fluorescent/photothermal dual-mode imaging enables accurate visualization of the therapeutic action in tumor sites. This study provides a facile strategy to construct self-assembled multimodal theranostic systems, and the functional protein-based theranostic system prepared holds great promise in multimodal cancer therapeutics.

Nanoclustered Cascaded Enzymes for Targeted Tumor Starvation and Deoxygenation-Activated Chemotherapy without Systemic Toxicity.

Intratumoral glucose depletion-induced cancer starvation represents an important strategy for anticancer therapy, but it is often limited by systemic toxicity, nonspecificity, and adaptive development of parallel energy supplies. Herein, we introduce a concept of cascaded catalytic nanomedicine by combining targeted tumor starvation and deoxygenation-activated chemotherapy for an efficient cancer treatment with reduced systemic toxicity. Briefly, nanoclustered cascaded enzymes were synthesized by covalently cross-linking glucose oxidase (GOx) and catalase (CAT) via a pH-responsive polymer. The release of the enzymes can be first triggered by the mildly acidic tumor microenvironment and then be self-accelerated by the subsequent generation of gluconic acid. Once released, GOx can rapidly deplete glucose and molecular oxygen in tumor cells while the toxic side product, i.e., H2O2, can be readily decomposed by CAT for site-specific and low-toxicity tumor starvation. Furthermore, the enzymatic cascades also created a local hypoxia with the oxygen consumption and reductase-activated prodrugs for an additional chemotherapy. The current report represents a promising combinatorial approach using cascaded catalytic nanomedicine to reach concurrent selectivity and efficiency of cancer therapeutics.

A traceable nanoplatform for enhanced chemo-photodynamic therapy by reducing oxygen consumption

Tumor hypoxia impedes the efficiencies of oxygen-dependent photodynamic therapy (PDT) and chemotherapy. Herein, we design a traceable nanoplatform (DOX/Met/BSA-HA-CDs) by reducing oxygen (O2) consumption to overcome the hypoxia-caused cancer therapy. Carbon dots (CDs) are used not only as a PDT agent but also applied for in vivo traceable imaging. Metformin (Met), a potent antihyperglycemic agent, to improve tumor oxygenation and enhance the efficiencies of hypoxia-caused cancer therapy. In the hypoxic tumor microenvironment, Met was released more rapidly than DOX, which is advantageous for improving hypoxic cancer to exert a better therapeutic efficiency. Ex vivo immunofluorescence staining revealed that the DOX/Met/BSA-HA-CDs nanoparticles greatly reduce O2 consumption in tumor site. Followed by in vivo synergistic treatment achieved considerably enhanced cancer therapeutic efficiency. This system holds great clinical promise as a traceable imaging approach to guide the improvement of PDT and chemotherapy efficiencies through utilizing a simple, safe method improved hypoxic tumor microenvironment.

Toward Normalization of the Tumor Microenvironment for Cancer Therapy.

The tumor microenvironment (TME) is a complex ecosystem, including blood vessels, immune cells, fibroblasts, extracellular matrix, cytokines, hormones, and so on. The TME differs from the normal tissue environment (NTE) in many aspects, such as tissue architecture, chronic inflammation, level of oxygen and pH, nutritional state of the cells, as well as tissue firmness. The NTE can inhibit the growth of cancer at the early tumorigenesis phase, whereas the TME promotes the growth of cancer in general, although it may have some anticancer effects. In particular, the TME plays a crucial role in the generation and maintenance of cancer stem cells, which lie at the root of cancer growth. Therefore, normalization of the TME to the NTE may inhibit cancer growth or improve cancer therapeutic efficiency. This review focuses on the recent emerging approaches for this normalization and the action mechanisms.

Tailored Surfaces on 2D Material: UFO‐Like Cyclodextrin‐Pd Nanosheet/Metal Organic Framework Janus Nanoparticles for Synergistic Cancer Therapy

AbstractThe development of novel Janus nanostructure with desired compositions and functionalities is essential for various applications, especially as drug delivery system to deliver multiple payloads with total different solubility. Here, a unidentified flying object (UFO)‐like cyclodextrin–palladium nanosheet/zeolitic imidazolate framework‐8 Janus nanoparticle (CD–PdNS/ZIF‐8 JNP) prepared via a selective coating of polyacrylic acid (PAA) on one of the flat surfaces of 2D PdNS followed by further formation of ZIF‐8 on a PAA template, and alternative modification of CDs on exposed PdNS surface is reported. The CD‐PdNS and PAA‐ZIF‐8 parts are designed to load hydrophobic10‐hydroxycamptothecin (HCPT) and hydrophilic doxorubicin (Dox) independently for synergistic chemotherapy (combination index = 0.65). Because of the broad near‐infrared (NIR) absorption band of PdNSs, the photothermal effect of UFO‐like CD‐PdNS/ZIF‐8 JNPs in NIR‐II biowindow is studied. The in vitro and in vivo results show that the dual‐drug loaded JNPs under a laser‐irradiation group present highest cancer therapeutic efficiency. The good performance is due to the synergistic chemotherapy and photothermal therapy in NIR‐II biowindow. This work significantly broadens the application prospects of metal–metal organic framework JNPs by rationally designing their compositions and discovering related physiochemical properties.

Multifunctional Supramolecular Materials Constructed from Polypyrrole@UiO-66 Nanohybrids and Pillararene Nanovalves for Targeted Chemophotothermal Therapy.

Multifunctional supramolecular nanomaterials capable of targeted and multimodal therapy hold great potential to improve the efficiency of cancer therapeutics. Herein, we report a proof-of-concept nanoplatform for effective chemophotothermal therapy via the integration of folic acid-based active targeting and supramolecular nanovalves-based passive targeting. Inspired by facile surface engineering and designable layer-by-layer assembly concept, we design and synthesize PPy@UiO-66@WP6@PEI-Fa nanoparticles (PUWPFa NPs) to achieve efficient synergistic chemophotothermal therapy, taking advantage of the desirable photothermal conversion capability of polypyrrole nanoparticles (PPy NPs) and high drug-loading capacity of hybrid scaffolds. Significantly, pillararene-based pseudorotaxanes as pH/temperature dual-responsive nanovalves allow targeted drug delivery in pathological environment with sustained release over 4 days, which is complementary to photothermal therapy, and folic acid-conjugated polyethyleneimine (PEI-Fa) at the outmost layer through electrostatic interactions is able to enhance tumor-targeting and therapeutic efficiency. Such PUWPFa NPs showed efficient synergistic chemophotothermal therapy of cervical cancer both in vitro and in vivo. The present strategy offers not only the distinctly targeted drug delivery and release, but also excellent tumor inhibition efficacy of simultaneous chemophotothermal therapy, opening a new avenue for effective cancer treatment.