Bacteria‐Assisted Selective Photothermal Therapy for Precise Tumor Inhibition

Photothermal therapy (PTT) has drawn extensive research attention as a promising approach for tumor treatment. In this study, a bacteria‐assisted strategy relying on the selective reduction of perylene diimide derivative based supramolecular complex (CPPDI) to radical anions (RAs) by Escherichia coli in hypoxic tumors is developed to realize highly precise PTT of tumors. Noninvasive E. coli are first injected intravenously for selectively accumulating and replicating in the tumor due to the hypoxia tropism. Then, CPPDI is loaded in a peptide‐hybrid matrix metalloproteinase‐2 (MMP‐2) responsive liposome (MRL) and injected intravenously. After accumulated and released from MRL in the tumor where MMP‐2 is overexpressed, CPPDI is reduced by E. coli in the hypoxic tumor environment to produce CPPDI RAs (CRAs), which serve as effective photothermal agents for tumor cells thermal ablation under near‐infrared light irradiation. Since E. coli accumulate and grow in tumor sites selectively, this strategy accurately limits the production of CRAs in tumors for highly selective PTT, which will find great potential for precise tumor inhibition.     

Multifunctional and Stimuli‐Responsive Polydopamine Nanoparticle‐Based Platform for Targeted Antimicrobial Applications

The rising threat of antimicrobial resistance is a crisis of a global scale. If not addressed, it can lead to health care system problems worldwide. This warrants alternative therapeutic approaches whose mechanism of action starkly differs from conventional antibiotic‐based therapies. Here, a multifunctional and stimuli‐responsive (NIR laser‐activated) antimicrobial platform is engineered by combining the intrinsic photothermal capability and excellent biocompatibility of polydopamine nanoparticles (PdNPs), with the membrane targeting and lytic activities of an antimicrobial peptide (AMP). The resulting PdNP‐AMP nanosystem can specifically target and destabilize the mechanical integrity of the outer membrane of Escherichia coli, as measured using the atomic force microscope. Furthermore, the laser‐induced nano‐localized heating of PdNP—in close proximity to the already compromised bacterial envelope—induces further membrane damage. This results in a more efficient, laser‐activated, bacterial killing action of PdNP‐AMP. The antimicrobial platform developed in this work is shown to be effective against a drug‐resistant E. coli. Overall, this work highlights the advantage and strength of combining multiple and coordinated biocidal mechanisms, into one nanomaterial‐based system and its promise in treating drug‐resistant pathogens.     

Precise Starving Therapy via Physiologically Dependent Photothermal Conversion Promoted Mitochondrial Calcification Based on Multi-Functional Gold Nanoparticles for Effective Tumor Treatment

Starving therapy based on tumor calcification has been considered as a promising strategy with high biosafety for tumor treatment. However, the limited calcium (Ca²⁺) concentration in/around tumor tissue as well as the slow and uncontrollable process of the physiological calcification are all challenges for its application. Herein, a sialic acid (SA, Ca²⁺ chelator), folic acid (FA, tumor targeting agent) and triphenylphosphine (TPP, mitochondrial targeting agent) co-modified gold nanoparticles (SFT-Au) are fabricated to take advantage of the abundant Ca²⁺ in mitochondria as well as the Ca²⁺ collection and Ca²⁺ dependent photothermal property of SFT-Au to achieve a precise and promoted calcification of tumor mitochondria for effective starving therapy. During therapy, the SFT-Au will first accumulate in tumor mitochondria through stepwise targeting processes medicated by FA and TPP. After that, the SA further binds with the over-expressed Ca²⁺ in tumor mitochondria to induce the aggregation of SFT-Au, which not only gathers Ca²⁺ to initiate the calcification of mitochondria, but in situ generates photothermal agent to perform photothermal conversion under 808 nm irradiation to promote the calcification, resulting in effective prohibition of the energy metabolism in tumor cells for starving therapy and continuously photothermal damage of tumor cells to enhance the therapeutic efficiency.     

Self‐Mineralized Photothermal Bacteria Hybridizing with Mitochondria‐Targeted Metal–Organic Frameworks for Augmenting Photothermal Tumor Therapy

A photothermal bacterium (PTB) is reported for tumor‐targeted photothermal therapy (PTT) by using facultative anaerobic bacterium Shewanella oneidensis MR‐1 (S. oneidensis MR‐1) to biomineralize palladium nanoparticles (Pd NPs) on its surface without affecting bacterial activity. It is found that PTB possesses superior photothermal property in near infrared (NIR) regions, as well as preferential tumor‐targeting capacity. Zeolitic imidazole frameworks‐90 (ZIF‐90) encapsulating photosensitizer methylene blue (MB) are hybridized on the surface of living PTB to further enhance PTT efficacy. MB‐encapsulated ZIF‐90 (ZIF‐90/MB) can selectively release MB at mitochondria and cause mitochondrial dysfunction by producing singlet oxygen (¹O₂) under light illumination. Mitochondrial dysfunction further contributes to adenosine triphosphate (ATP) synthesis inhibition and heat shock proteins (HSPs) down‐regulated expression. The PTB‐based therapeutic platform of PTB@ZIF‐90/MB demonstrated here will find great potential to overcome the challenges of tumor targeting and tumor heat tolerance in PTT.     

Stimuli‐Responsive Scaffold for Breast Cancer Treatment Combining Accurate Photothermal Therapy and Adipose Tissue Regeneration

Development of new therapeutic scaffolds to selectively destruct tumors under gentle conditions meanwhile promoting adipose tissue formation would be a promising strategy for clinical treatment of breast cancer. Herein, a stimuli‐responsive scaffold composed of polyacrylic acid‐g‐polylactic acid (PAA‐g‐PLLA) modified graphene oxide (GO) with a cleavable bond in between (GO‐PAA‐g‐PLLA), gambogic acid (GA), and polycaprolactone (PCL) is fabricated and then preseeded on adipose‐derived stem cells (ADSCs) for breast cancer treatment. This GO–GA‐polymer scaffold is able to simultaneously perform pH‐triggered low temperature (45 °C) photothermal therapy to selectively induce the apoptosis of tumor cells and significantly improve ADSCs growth without any photothermal damage. The low‐temperature photothermal therapy of the scaffolds can induce more than 95% of cell death for human breast cancer (MCF‐7) in vitro, which further completely inhibits tumor growth and finally eliminates tumor tissue in mice. Meanwhile, the prepared GO–GA‐polymer scaffold possesses the improved capability to stimulate the differentiation of ADSCs into adipocytes by upregulating adipo‐related gene expression, and significantly promotes new adipose tissue formation whether with or without NIR irradiation. These results successfully demonstrate that the prepared GO–GA‐polymer scaffolds with bifunctional properties will be a promising candidate for clinical cases involving both tumor treatment and tissue engineering.     

An Engineered Mannoside Presenting Platform: Escherichia coli Adhesion under Static and Dynamic Conditions

The study of the adhesion mechanisms of pathogens to host tissues has gained increased interest as bacterial adhesion is involved in the early stages of surface colonization and infection. Here we describe a platform to study the specific binding of the bacterium Escherichia coli (E. coli) K‐12 strain to molecularly well‐defined surfaces mimicking cellular interfaces. This approach uses a poly(ethylene glycol) brush interface, which displays synthetic determinants of the high mannose N‐linked glycans in a range of densities (3.8 × 10⁴–1.6 × 10⁵ mannosides µm^?2) for the investigation of multivalent interactions with bacteria. The bacterial attachment is mediated by specific interactions between the adhesive protein FimH located on the tip of the bacterial type 1 pili and the mannosylated surfaces. With synthetically engineered mannoses, it is found that the number of strongly adhering bacteria is co‐regulated by many structural physical parameters. Beyond the dependency on carbohydrate density, higher numbers of E. coli attach to the branched trimannose Man(α1–3)(Man(α1–6))Man compared to the monomannose, while larger oligomannoses exposing Man(α1–2) Man at their non reducing end show low binding capacity. The linker used between the mannose moiety and PEG is also affecting the binding efficacy of E. coli. The (hydrophobic) propyl linker results in higher bacteria numbers in comparison to the (hydrophilic) tri(EG), likely a consequence of additional stabilization of the binding complex by hydrophobic interactions. Furthermore, differences are observed in bacteria attachment between stagnant and flow conditions that depend on the type of mannose ligand. Finally, a photolithographic resist lift‐off combined with site‐selective assembly of the glycopolymers is used to produce micropatterns with bacteria colonies confined to defined areas and at controlled colony numbers.     

Antibody Engineered Platelets Attracted by Bacteria-Induced Tumor-Specific Blood Coagulation for Checkpoint Inhibitor Immunotherapy

Bacteria can act as a promising anti-tumor platform due to their specific targeting capacity to the tumor microenvironment. In this study, it is discovered that intravenous administration of Escherichia coli TOP10 induces rapid and intense blood coagulation in tumor tissues instead of normal tissues. It is demonstrated that E. coli TOP10 can act as an activator of a coagulation cascade to trigger abnormal hemorrhage, blood coagulation, and inflammation with abundant macrophages recruitment in tumors. In addition, the recruited macrophages are principally polarized by lipopolysaccharide in the bacterial wall to the anti-tumor M1-like phenotype. Based on the above finding, coagulation-tropism blood platelets decorated with CD47 antibodies (Anti-CD47), which possess tropism for bacteria-treated tumors are further prepared. As a result, Anti-CD47 blocks the “don't eat me” signal from tumor cells, consequently promoting the phagocytosis of polarized M1-like phenotype macrophages for tumor cells. This manipulation of local blood coagulation in tumors may find great potential for accurately delivering immune checkpoint inhibitors and facilitating tumor immunotherapy.     

Long‐Circulating Drug‐Dye‐Based Micelles with Ultrahigh pH‐Sensitivity for Deep Tumor Penetration and Superior Chemo‐Photothermal Therapy

Nanocarriers for chemo‐photothermal therapy suffer from insufficient retention at the tumor site and poor penetration into tumor parenchyma. A smart drug‐dye‐based micelle is designed by making the best of the structural features of small‐molecule drugs. P‐DOX is synthesized by conjugating doxorubicin (DOX) with poly(4‐formylphenyl methacrylate‐co‐2‐(diethylamino) ethyl methacrylate)‐b‐polyoligoethyleneglycol methacrylate (P(FPMA‐co‐DEA)‐b‐POEGMA) via imine linkage. Through the π–π stacking interaction, IR780, a near‐infrared fluorescence dye as well as a photothermal agent, is integrated into the micelles (IR780‐PDMs) with the P‐DOX. The IR780‐PDMs show remarkably long blood circulation (t_1/2β = 22.6 h). As a result, a progressive tumor accumulation and retention are presented, which is significant to the sequential drug release. Moreover, when entering into a moderate acidic tumor microenvironment, IR780‐PDMs can dissociate into small‐size conjugates and IR780, which obviously increases the penetration depth of drugs, and then improves the lethality to deep‐seated tumor cells. Owing to the high delivery efficiency and superior chemo‐photothermal therapeutic efficacy of IR780‐PDMs, 97.6% tumor growth in the A549 tumor‐bearing mice is suppressed with a low dose of intravenous injection (DOX, 1.5 mg kg^?1; IR780, 0.8 mg kg^?1). This work presents a brand‐new strategy for long‐acting intensive cancer therapy.     

Optimization of Prussian Blue Coated NaDyF4:x%Lu Nanocomposites for Multifunctional Imaging‐Guided Photothermal Therapy

Imaging‐guided photothermal therapy based on functional nanomaterials has recently received significant attention and the selection of functional materials with optimal imaging and therapy effect is extremely important. In this work, NaDyF₄‐based nanoparticles with varying size are synthesized by doping with different amounts of lutetium ions. To obtain an optimized material, the influence factor of magnetic resonance, X‐ray attenuation, and photothermal properties are discussed in detail. Then, NaDyF₄:50%Lu@Prussian blue (PB) nanocomposite is selected as the optimal functional material for T₁‐ and T₂‐weighted magnetic resonance imaging, X‐ray computed tomography, and photothermal imaging‐guided photothermal therapy of tumor on a small animal model, and the treatment is applied with good results. Studies also suggest that the NaDyF₄:50%Lu@PB nanocomposites are biocompatibile. The selection of an optimal material from a multi‐perspective study has provided an incentive for the development of an assortment of novel multifunctional materials for early cancer multifunctional diagnosis and imaging‐guided photothermal therapy.     

Molecular Evolution of Acceptor–Donor–Acceptor-type Conjugated Oligomer Nanoparticles for Efficient Photothermal Antimicrobial Therapy

Infectious diseases (such as wound infections) caused by pathogenic microorganisms can lead to serious consequences and even threaten life. The emergence of drug-resistant bacteria has severely prevented the validity of traditional antibiotics. Therefore, developing novel antimicrobial strategies without drug-resistant holds great promise for maximizing efficacy and minimizing the risk of drug-resistance of resistant bacterial infections. Herein, near-infrared (NIR)-absorbing A–D–A type conjugated oligomers with a tunable backbone are designed and synthesized for regulating their photothermal conversion. After being assembled into nanoparticles, the conjugated oligomer CP-F8P nanoparticles (NPs) containing a strong electron-donating component show the strongest photothermal conversion efficiency of 81.6%. The low concentration of CP-F8P NPs receive over 99% of antimicrobial efficiency against Amp^r E. coli, S. aureus, and C. albicans upon NIR irradiation, and the phototherapy treatment of CP-F8P NPs can effectively promote wound healing in diabetic mice with good biocompatibility. This work provides ideas for the design of efficient NIR-activated antimicrobial reagents against drug-resistant microbial infections.     

Core–Satellite Mesoporous Silica–Gold Nanotheranostics for Biological Stimuli Triggered Multimodal Cancer Therapy

A core–satellite nanotheranostic agent with pH‐dependent photothermal properties, pH‐triggered drug release, and H₂O₂‐induced catalytic generation of radical medicine is fabricated to give a selective and effective tumor medicine with three modes of action. The nanocomplex (core–satellite mesoporous silica–gold nanocomposite) consists of amino‐group‐functionalized mesoporous silica nanoparticles (MSN‐NH₂) linked to L‐cysteine‐derivatized gold nanoparticles (AuNPs‐Cys) with bridging ferrous iron (Fe²⁺) ions. The AuNPs‐Cys serve as both removable caps that control drug release (doxorubicin) and stimuli‐responsive agents for selective photothermal therapy. Drug release and photothermal therapy are initiated by the cleavage of Fe²⁺ coordination bonds at low pH and the spontaneous aggregation of the dissociated AuNPs‐Cys. In addition, the Fe²⁺ is able to catalyze the decomposition of hydrogen peroxide abundant in cancer cells by a Fenton‐like reaction to generate high‐concentration hydroxyl radicals (·OH), which then causes cell damage. This system requires two tumor microenvironment conditions (low pH and considerable amounts of H₂O₂) to trigger the three therapeutic actions. In vivo data from mouse models show that a tumor can be completely inhibited after two weeks of treatment with the combined chemo‐photothermal method; the data directly demonstrate the efficiency of the MSN–Fe–AuNPs for tumor therapy.     

Dendritic Fe3O4@Poly(dopamine)@PAMAM Nanocomposite as Controllable NO‐Releasing Material: A Synergistic Photothermal and NO Antibacterial Study

Nowadays, antibiotic abuse increases the emergence of multidrug‐resistant bacterial strains, which is the major reason for the failure of conventional antibiotic therapies. Therefore, developing novel antibacterial materials or therapies is an urgent demand. In the present study, photothermal and NO‐releasing properties are integrated into a single nanocomposite to realize more efficient bactericidal effects. To this end, polydopamine (PDA) coated iron oxide nanocomposite (Fe₃O₄@PDA) is used as a photoconversion agent and the core, first three generation dendritic poly(amidoamine) (PAMAM‐G3) is grafted on the surface of Fe₃O₄@PDA, and subsequently NO is loaded with the formation of NONOate. The resultant Fe₃O₄@PDA@PAMAM@NONOate displays controllable NO release property under intermittent 808 nm laser irradiation and excellent bacteria‐separation efficiency. Moreover, excellent synergistic photothermal and NO antibacterial effects are observed against both Gram‐negative Escherichia coli and Gram‐positive Staphylococcus aureus, where bacterial viability and biofilm are significantly reduced. An antibacterial mechanism study reveals that the materials first adsorb onto the bacterial membrane, then cause damage to the membrane by the increased local temperature and the released NO under laser irradiation conditions, finally leak the intracellular components like DNA and induce bacteria death. The work provides a novel way for designing of antibacterial materials with higher efficiency.     

Protease-Activatable Nanozyme with Photoacoustic and Tumor-Enhanced Magnetic Resonance Imaging for Photothermal Ferroptosis Cancer Therapy

Despite the promise of ferrotherapy in cancer treatment, current ferrous therapeutics suffer from compromised antitumor ferroptosis efficacy and low specificity for tumors. Herein, a protease-activatable nanozyme (Fe₃O₄@Cu_1.77Se) is reported for photoacoustic and tumor-enhanced magnetic resonance imaging (MRI)-guided second near-IR photothermal ferroptosis cancer therapy. Fe₃O₄@Cu_1.77Se remains stable in physiological conditions, but disintegrates to increase reactive intratumoral ferrous supply for elevated hydroxyl radical generation by Fenton reaction and GSH depletion in response to overexpressed matrix metalloproteinases in tumor microenvironment, leading to amplified ferroptosis of tumor cells as well as enhanced T₂-weighted MRI contrast. Further integration with second near-IR photoirradiation to generate localized heat not only triggers effective photothermal therapy and photoacoustic imaging but more importantly, potentiates Fenton reaction to promote ferroptotic tumor cell death. Such synergism leads to the polarization of tumor-associated macrophage from the tumor-promoting M2 type to the tumor-killing M1 type, and induces the immunogenic cells death of tumor cells, which in turn promotes the maturation of dendritic cells and infiltration of cytotoxic T lymphocytes in tumor, contributing to significant tumor suppression. This study presents a novel activatable ferrous nanotheranostics for spatial-temporal control over antitumor ferroptosis responses.     

Construction of Chitosan‐Based Hydrogel Incorporated with Antimonene Nanosheets for Rapid Capture and Elimination of Bacteria

To elaborately construct a novel and efficient photothermal antibacterial nanoplatform is a promising strategy for treating bacterial wound infections. In this work, a composite hydrogel (CS/AM NSs hydrogel) with outstanding antibacterial ability is constructed by incorporating antimonene nanosheets (AM NSs) with extraordinary photothermal properties into the network structure of chitosan (CS). When cultured with bacteria, the CS/AM NSs hydrogel can gather bacteria on the surface through the interaction of CS with the bacterial cell membrane. Subsequently, the intrinsic bactericidal property of CS will kill some of the bacteria. After the introduction of near‐infrared laser, the AM NSs effectively convert light energy into localized heat to eliminate residual bacteria. By virtue of the synergistic action between the capture effect of CS and the photothermal effect of AM NSs, the CS/AM NSs hydrogel shows predominant antibacterial behavior against Escherichia coli and Staphylococcus aureus. In vitro assay and in vivo tests of infected full‐thickness defect wound healing confirm the satisfactory biocompatibility and antibacterial ability. Overall, this work reveals that the CS/AM NSs hydrogel holds great potential as a broad‐spectrum antibacterial wound dressing for treating bacteria‐infected wounds. Additionally, this is the first report of the application of AM NSs in the field of antibacterial treatment.     

NIR‐Laser‐Controlled Hydrogen‐Releasing PdH Nanohydride for Synergistic Hydrogen‐Photothermal Antibacterial and Wound‐Healing Therapies

For decades, hydrogen (H₂) gas has been recognized as an excellent antioxidant molecule that holds promise in treating many diseases like Alzheimer's, stroke, cancer, and so on. For the first time, active hydrogen is demonstrated to be highly efficient in antibacterial, antibiofilm, and wound‐healing applications, in particular when used in combination with the photothermal effect. As a proof of concept, a biocompatible hydrogen‐releasing PdH nanohydride, displaying on‐demand controlled active hydrogen release property under near‐infrared laser irradiation, is fabricated by incorporating H₂ into Pd nanocubes. The obtained PdH nanohydride combines both merits of bioactive hydrogen and photothermal effect of Pd, exhibiting excellent in vitro and in vivo antibacterial activities due to its synergistic hydrogen‐photothermal therapeutic effect. Interestingly, combinational hydrogen‐photothermal treatment is also proved to be an excellent therapeutic methodology in healing rats' wound with serious bacterial infection. Moreover, an in‐depth antibacterial mechanism study reveals that two potential pathways are involved in the synergistic hydrogen‐photothermal antibacterial effect. One is to upregulate bacterial metabolism relevant genes like dmpI, narJ, and nark, which subsequently encode more expression of oxidative metabolic enzymes to generate substantial reactive oxygen species to induce DNA damage and another is to cause severe bacterial membrane damage to release intracellular compounds like DNA.     

Polydopamine Sensors of Bacterial Hypoxia via Fluorescence Coupling

Biological catecholamines play critical physiological roles in various parts of the human body, namely, the skin and brain. In the skin, an oxygen-contacting and oxygen-abundant body part, catecholamine molecules are oxidatively polymerized, becoming melanin. In contrast, the brain is an oxygen-demanding organ that suppresses catecholamine oxidation. Catecholamine oxidative polymerization, also known as polydopamine (or dopamine–melanin) formation, can be finely controlled by bacterial growth. Under exponential growth of Escherichia coli, a process that requires large amounts of oxygen, dopamine polymerization is significantly inhibited. In contrast, under steady-state growth, polydopamine is formed due to the abundance of oxygen which is not actively consumed by E. coli. This polydopamine-oxygen relationship is further demonstrated by using fluorescent dextran nanoparticles (FDNPs) as sensors, whose fluorescence is quenched by polydopamine formation. Thus, FDNP fluorescence can be precisely controlled by dopamine concentration, incubation time, and bacterial number. The cascade coupling of E. coli growth—oxygen level—polydopamine—fluorescence can also be used to detect the antibiotic-resistant bacteria, New Delhi metallo-beta-lactamase 1-positive (NDM1+) E. coli. This method not only uncovers the unique role played by biological catecholamine in a living system, but also presents a diagnostic assay for detecting bacterial growth and antibiotic susceptibility.     

A Universal and Ultrastable Mineralization Coating Bioinspired from Biofilms

A simple and universal method for manufacturing a mineralization coating on various surfaces is developed using a biofilm‐based material obtained from engineered curli nanofibers. The amyloid protein (CsgA) is the main proteinaceous component in the Escherichia coli (E. coli) biofilm, which can withstand detergents in the harsh environment. The peptide sequence DDDEEK is bioinspired from salivary acquired pellicles in the dental plaque biofilm, having a strong ability to absorb mineral ions and induce the formation of biominerals. The bioinspired coating is successfully secreted by the engineered E. coli, which is transformed with a recombinant plasmid for expression with T7 promoter (PET), namely PET‐22b‐CsgA‐DDDEEK plasmid. The uniform coating can bear shear force and stay on virtually any type of material surface for at least one month. Moreover, the coated slices had a good mineralization performance and better stability than hydroxyapatite (HA)‐spray slices. Furthermore, MG63 cells on the bioactive HA layer induced by the coating possess a better growth capacity than those on the commercial product Matrigel. The animal experiment results suggest that the coated Ti₆Al₄V screws with induced HA present better osteogenicity and osseointegration than HA‐sprayed screws after 12 weeks, as well as no extra immunogenicity. Thus, the coating is highly promising for biomedical applications.     

Synergistic Oxidative Damage with Gene Therapy Potentiates Targeted Sterilization of Broad-Spectrum Microorganisms

Nanoparticle-based approaches addressed the barriers to antibiotic resistance faced by traditional antimicrobial agents. However, nanotherapies against multibacterial infections still suffered from the lack of broad-spectrum targeting ability and the mono-inhibition pathway. In this study, a multimodality therapeutic nanoplatform (denoted as Asza) is introduced, which combines specific recognition, synergistic oxidative damage, and gene therapy, to effectively inhibit the emergence of bacterial resistance, achieving broad-spectrum sterilization activity against two Gram-positive (B. subt, S. epider) and two Gram-negative bacteria (E. coli, E. aero). In addition to the oxidative damage generated from gold nanoclusters, DNA aptamer, and CRISPR-Cas modules are combined in the Asza to recognize multiple bacteria and cleave the ftsz gene with high specificity, allowing precision treatment of multibacterial infections without damaging surrounding healthy cells. Furthermore, multimodal antimicrobial strategies can reduce the risk of the generation of bacterial resistance to single-modality therapy and significantly boost the efficiency of antibacterial therapy. This study offers a promising approach to advance the applications of nanomaterials in clinical antimicrobial therapy.     

Fabricating Aptamer‐Conjugated PEGylated‐MoS2/Cu1.8S Theranostic Nanoplatform for Multiplexed Imaging Diagnosis and Chemo‐Photothermal Therapy of Cancer

Fabricating theranostic nanoparticles combining multimode disease diagnosis and therapeutic has become an emerging approach for personal nanomedicine. However, the diagnostic capability, biocompatibility, and therapeutic efficiency of theranostic nanoplatforms limit their clinic widespread applications. Targeting to the theme of accurate diagnosis and effective therapy of cancer cells, a multifunctional nanoplatform of aptamer and polyethylene glycol (PEG) conjugated MoS₂ nanosheets decorated with Cu_1.8S nanoparticles (ATPMC) is developed. The ATPMC nanoplatform accomplishes photoluminescence imaging, photoacoustic imaging, and photothermal imaging for in vitro and in vivo tumor cells imaging diagnosis. Meanwhile, the ATPMC nanoplatform facilitates selective delivery of gene probe to detect intracellular microRNA aberrantly expressed in cancer cells and anticancer drug doxorubicin (DOX) for chemotherapy. Moreover, the synergistic interaction of MoS₂ and Cu_1.8S renders the ATPMC nanoplatform with superb photothermal conversion efficiency. The ATPMC nanoplatform loaded with DOX displays near‐infrared laser‐induced programmed chemotherapy and advanced photothermal therapy, and the targeted chemo‐photothermal therapy presents excellent antitumor efficiency.