Combination Of Phototherapy Research Articles

Redox-Inducible Radiomimetic Photosensitizers Selectively Suppress Cancer Cell Proliferation by Damaging DNA through Radical Cation Chemistry.

Radiotherapy leverages ionizing radiation to kill cancer cells through direct and indirect effects, and direct effects are considered to play an equal or greater role. Several photosensitizers have been developed to mimic the direct effects of radiotherapy, generating radical cations in DNA models, but none has been applied in cellular studies. Here, we design a radiomimetic photosensitizer, producing DNA radical cations in cells for the first time. To reduce adverse effects, several redox-inducible precursors are prepared as cancer cells have elevated levels of GSH and H2O2. These precursors respond to GSH or H2O2, releasing the active photosensitizer that captures DNA abasic (AP) sites and generates DNA radical cations upon photolysis, without disrupting the redox state of cells. DNA radical cations migrate freely and are eventually trapped by H2O and O2 to yield DNA lesions, thus triggering DNA damage response. Our study suggests that direct effects of radiotherapy suppress cancer cell proliferation mainly by inducing G2/M phase cell cycle arrest, rather than promoting apoptosis. Synergistic effects of the precursor and chemotherapeutic agents are also observed in combination phototherapy. Beyond highlighting an alternative strategy for phototherapy, this proof-of-concept study affords a facile cellular platform to study the direct effects of radiotherapy.

Redox‐Inducible Radiomimetic Photosensitizers Selectively Suppress Cancer Cell Proliferation by Damaging DNA through Radical Cation Chemistry

AbstractRadiotherapy leverages ionizing radiation to kill cancer cells through direct and indirect effects, and direct effects are considered to play an equal or greater role. Several photosensitizers have been developed to mimic the direct effects of radiotherapy, generating radical cations in DNA models, but none has been applied in cellular studies. Here, we design a radiomimetic photosensitizer, producing DNA radical cations in cells for the first time. To reduce adverse effects, several redox‐inducible precursors are prepared as cancer cells have elevated levels of GSH and H2O2. These precursors respond to GSH or H2O2, releasing the active photosensitizer that captures DNA abasic (AP) sites and generates DNA radical cations upon photolysis, without disrupting the redox state of cells. DNA radical cations migrate freely and are eventually trapped by H2O and O2 to yield DNA lesions, thus triggering DNA damage response. Our study suggests that direct effects of radiotherapy suppress cancer cell proliferation mainly by inducing G2/M phase cell cycle arrest, rather than promoting apoptosis. Synergistic effects of the precursor and chemotherapeutic agents are also observed in combination phototherapy. Beyond highlighting an alternative strategy for phototherapy, this proof‐of‐concept study affords a facile cellular platform to study the direct effects of radiotherapy.

NIR-Absorbing Tetraphenylethene-Containing bisBODIPY Nanoplatforms Demonstrate Effective Lysosome-Targeting and Combinational Phototherapy.

Photosensitizer-based phototherapies, including photodynamic therapy (PDT) and photothermal therapy (PTT), offer safe treatment modalities for tumor ablation with spatiotemporal precision. After photons are absorbed, PDT creates localized chemical damage by generating reactive oxygen species (ROS), while PTT induces localized thermal damage. However, PDT still faces hypoxic tumor challenges, while PTT encounters issues related to heat resistance and potential overheating. The combination of PDT and PTT shows great potential as an effective anticancer strategy. By targeting lysosomes with carefully designed phototherapeutic reagents for combined phototherapy, rapid dysfunction and cell death in cancer cells can be induced, showing promise for cancer treatment. Herein, two α-α-linked bisBODIPYs with tetraphenylethene (TPE) moieties are designed and synthesized. These TPE-substituted bisBODIPYs expand the absorption into NIR range (λmaxabs/λmaxem ∼ 740/810 nm) and confer aggregation-induced emission (AIE) activity (λmaxem ∼ 912 nm). Moreover, these bisBODIPYs self-assemble with surfactant F-127 into nanoparticles (NPs), which efficiently generate ROS (1O2 and •OH) in both solution and cellular environments and demonstrate superior photothermal conversion efficiencies (η ∼ 68.3%) along with exceptional photothermal stability. More importantly, these NPs showed lysosomal targeting and remarkable tumor ablation in cellular and murine models, indicating their potential in precision tumor therapy.

NIR-II AIE Luminogen-Based Erythrocyte-Like Nanoparticles with Granuloma-Targeting and Self-Oxygenation Characteristics for Combined Phototherapy of Tuberculosis.

Tuberculosis, a fatal infectious disease caused by Mycobacterium tuberculosis (M.tb), is difficult to treat with antibiotics due to drug resistance and short drug half-life. Phototherapy represents a promising alternative to antibiotics in combating M.tb. Exploring an intelligent material allowing effective tuberculosis treatment is definitely appealing, yet a significantly challenging task. Herein, an all-in-one biomimetic therapeutic nanoparticle featured by aggregation-induced second near-infrared emission, granuloma-targeting, and self-oxygenation is constructed, which can serve for prominent fluorescence imaging-navigated combined phototherapy toward tuberculosis. After camouflaging the biomimetic erythrocyte membrane, the nanoparticles show significantly prolonged blood circulation and increased selective accumulation in tuberculosis granuloma. Upon laser irradiation, the loading photosensitizer of aggregation-induced emission photosensitizer elevates the production of reactive oxygen species (ROS), causing M.tb damage and death. The delivery of oxygen to relieve the hypoxic granuloma microenvironment supports ROS generation during photodynamic therapy. Meanwhile, the photothermal agent, Prussian blue nanoparticles, plays the role of good photothermal killing effect on M.tb. Moreover, the growth and proliferation of granuloma and M.tb colonies are effectively inhibited in the nanoparticle-treated tuberculous granuloma model mice, suggesting the combined therapeutic effects of enhancing photodynamic therapy and photothermal therapy.

Impact of Combined Phototherapy and Melanocyte Transplantation on Indicators of Vitiligo Activity.

To investigate the effect of phototherapy combined with melanocyte transplantation on the activity index of vitiligo. One hundred twenty patients with stable vitiligo were selected and divided into 2 groups: phototherapy group (n = 60) and phototherapy combined with melanocyte therapy group (n = 60). Patients' vitiligo activity scores before and 6 months after treatment, patients' skin pigmentation responses 6 months after treatment, and patients' new Koebner cases 6 months after treatment were compared. The expression of tyrosinase and Melan-A in the skin samples was analyzed by immunohistochemistry. The effect of skin surface repigmentation in the observation group was better than that in the control group (p < .05). The expression of tyrosinase and Melan-A in the observation group was higher than that in the control group (p < .05), indicating that the combined treatment could enhance the function of melanocytes. After 6 months of treatment, the incidence of the Koebner phenomenon in the observation group was lower than that in the control group (p < .05). The combination of phototherapy and melanocyte transplantation can obviously improve the activity index of vitiligo, slow down the spread of white spots, reduce the formation of new white spots, and reduce the occurrence of the Koebner phenomenon.

Combination of phototherapy for treatment of labial necrotizing lesion

Lip necrotizing lesions are painful, complex to heal, and negatively impact the patient’s orofacial condition. The present study reports a clinical case of a necrotizing lesion on the lower lip in a 38-year-old male patient, previously healthy, f ive days after receiving the first dose of the SARS-COV-2 vaccine, with an initial diagnosis of labial herpes zoster, with secondary infection and unsatisfactory response to clinical treatment. After debridement of the necrotic tissue, followed by a combination of antimicrobial photodynamic therapy (aPDT), photobiomodulation therapy (PBMT) and hydrofiber dressing with silver, the patient evolved with complete healing of the lip lesion and satisfactory restoration of orofacial functions after 7 days. According to the present case report, this combination of phototherapy modalities suggests to be a promising tool for the treatment of necrotizing labial lesions.

Upconversion dual-photosensitizer-expressing bacteria for near-infrared monochromatically excitable synergistic phototherapy.

Synergistic phototherapy stands for superior treatment prospects than a single phototherapeutic modality. However, the combined photosensitizers often suffer from incompatible excitation mode, limited irradiation penetration depth, and lack of specificity. We describe the development of upconversion dual-photosensitizer-expressing bacteria (UDPB) for near-infrared monochromatically excitable combination phototherapy. UDPB are prepared by integrating genetic engineering and surface modification, in which bacteria are encoded to simultaneously express photothermal melanin and phototoxic KillerRed protein and the surface primary amino groups are derived to free thiols for biorthogonal conjugation of upconversion nanoparticles. UDPB exhibit a near-infrared monochromatic irradiation-mediated dual-activation characteristic as the photothermal conversion of melanin can be initiated directly, while the photodynamic effect of KillerRed can be stimulated indirectly by upconverted visible light emission. UDPB also show living features to colonize hypoxic lesion sites and inhibit pathogens via bacterial community competition. In two murine models of solid tumor and skin wound infection, UDPB separately induce robust antitumor response and a rapid wound healing effect.

Midbrain FA initiates neuroinflammation and depression onset in both acute and chronic LPS-induced depressive model mice

Both exogenous gaseous and liquid forms of formaldehyde (FA) can induce depressive-like behaviors in both animals and humans. Stress and neuronal excitation can elicit brain FA generation. However, whether endogenous FA participates in depression occurrence remains largely unknown. In this study, we report that midbrain FA derived from lipopolysaccharide (LPS) is a direct trigger of depression. Using an acute depressive model in mice, we found that one-week intraperitoneal injection (i.p.) of LPS activated semicarbazide-sensitive amine oxidase (SSAO) leading to FA production from the midbrain vascular endothelium. In both in vitro and in vivo experiments, FA stimulated the production of cytokines such as IL-1β, IL-6, and TNF-α. Strikingly, one-week microinfusion of FA as well as LPS into the midbrain dorsal raphe nucleus (DRN, a 5-HT-nergic nucleus) induced depressive-like behaviors and concurrent neuroinflammation. Conversely, NaHSO3 (a FA scavenger), improved depressive symptoms associated with a reduction in the levels of midbrain FA and cytokines. Moreover, the chronic depressive model of mice injected with four-week i.p. LPS exhibited a marked elevation in the levels of midbrain LPS accompanied by a substantial increase in the levels of FA and cytokines. Notably, four-week i.p. injection of FA as well as LPS elicited cytokine storm in the midbrain and disrupted the blood–brain barrier (BBB) by activating microglia and reducing the expression of claudin 5 (CLDN5, a protein with tight junctions in the BBB). However, the administration of 30 nm nano-packed coenzyme-Q10 (Q10, an endogenous FA scavenger), phototherapy (PT) utilizing 630-nm red light to degrade FA, and the combination of PT and Q10, reduced FA accumulation and neuroinflammation in the midbrain. Moreover, the combined therapy exhibited superior therapeutic efficacy in attenuating depressive symptoms compared to individual treatments. Thus, LPS-derived FA directly initiates depression onset, thereby suggesting that scavenging FA represents a promising strategy for depression treatment.

Multifunctional Nanoplatform for Single NIR Laser-Regulated Efficient PDT/PTT/Chemotherapy.

The combination of phototherapy and chemotherapy with superior advantages is a promising strategy for cancer therapy. However, combination therapy is generally regulated by two different wavelengths of light or other stimuli, which results in complex operations and inevitable systemic side effects, even affecting therapeutic efficacy. Herein, we design a signal NIR light-regulated nanoplatform via the self-assembly process of reactive oxygen species (ROS)-sensitive prodrug (DTD), human serum albumin (HSA), and IR780 for combined photothermal/photodynamic therapy and chemotherapy. Upon 808 nm laser irradiation, IR780 in nanoparticles generates abundant ROS and a significant photothermal effect to achieve photothermal/photodynamic therapy. Meanwhile, the generating ROS further cleans up the thioketal link to release DOX for chemotherapy. Hence, signal NIR light can effectively control the process of combination therapy. In vivo and in vitro experiment results demonstrate that the multifunctional nanoparticles exhibit excellent antitumor efficacy via the combination of phototherapy and chemotherapy controlled by a signal NIR laser. Overall, the signal NIR light-regulated nanoparticles with combination therapy performance provide a versatile platform for enhancing antitumor efficacy.

The Effectiveness Of Combination Vitamin D With Phototherapy For Vitiligo Treatment

Vitiligo represents a pigmentary skin disorder that impacts the layers of the skin, characterized by the absence of pigmentary cells in the epidermis, which causes the body to develop white patches and macules. However, additional research is necessary to comprehensively grasp the mechanisms that can be obtained using vitamin D with phototherapy for vitiligo treatment. Current evidence indicates that vitamin D substantially influences keratinocytes and melanocytes' activities through various mechanisms. Therefore, this literature review was organized to assess the effectiveness of combining vitamin D with phototherapy for vitiligo treatment. A search was conducted across four electronic journal databases: Google Scholar, PubMed, Taylor &amp; Francis, and ScienceDirect. Inclusion criteria involved studies with vitiligo respondents, explaining the effectiveness of combining vitamin D with phototherapy for vitiligo treatment and detailing the benefits or harms of using this combination in vitiligo patients. Only five studies met the specified criteria and are consequently considered deserving of further assessment. The combination of phototherapy and vitamin D is postulated to manage vitiligo effectively. Phototherapy enhances repigmentation, ensuring a harmonious color reconciliation with the innate skin tone. Simultaneously, Vitamin D assumes a pivotal role in modulating the activity of keratinocytes and melanocytes, operating through diverse mechanisms. Based on this article review, it can be concluded that phototherapy with vitamin D is more effective in treating vitiligo than phototherapy only.

Vitiligo: Current Therapies and Future Treatments.

The current management of vitiligo remains challenging; however, different strategies can be proposed to patients with a good efficacy in many cases. First, it is important to identify patients in the active phase of the disease because treatment should start as soon as possible to halt its progression. For patients with a stable disease, the treatment strategy is now well-stratified and is based on a combination of phototherapy (natural or in a cabin) and topical immunomodulatory agents. Surgical treatments are useful for localized and stable vitiligo, as well as for segmental vitiligo. Depigmentation remains indicated in very extensive forms. The recent approval of topical ruxolitinib cream in both the US and Europe brings new approaches for the management of vitiligo and paves the way for the development of new topical or oral targeted drugs.

Efficacy and safety of compound glycyrrhizin in combination with conventional therapy in treatment of vitiligo: A systematic review and meta-analysis of randomized controlled trials.

Vitiligo is an acquired chronic depigmentary disorder affecting approximately 0.5% to 1% of individuals worldwide. The compound glycyrrhizin (CG), a complementary medicine, has been reported for treatment of vitiligo, but the evidence has not been systematically evaluated. We systematically assessed the efficacy and safety of CG in combination with conventional therapy for the treatment of vitiligo. We searched Embase, Web of Science, PubMed, The Cochrane Library, Chinese BioMedical Literature Database (CBM), Wanfang Data, China National Knowledge Infrastructure (CNKI), and VIP information from inception to July 2022. Randomized controlled trials comparing CG combined with conventional therapy with conventional therapy alone for vitiligo were included in our analysis. The primary outcome was treatment response, which defined as >50% repigmentation rate of vitiligo after treatment. The secondary outcome was incidence of adverse events. Meta-analysis was performed using the Review Manager 5.4 software. Statistical heterogeneity was evaluated with chi-square and I2 statistics, dichotomous data were expressed as risk ratios (RR) with 95% confidence intervals using the Mantel-Haenszal method. Thirty-nine studies enrolling with 3994 participants were subjected to this review. The results of our meta-analysis indicated that addition of CG had superior effectiveness on repigmentation rate than phototherapy (RR = 1.28; P < .001), immunosuppressant (RR = 1.76; P < .001), traditional Chinese medicine (RR = 1.38; P < .001), combination of phototherapy and immunosuppressant (RR = 1.42; P < .001), and combination of phototherapy and traditional Chinese medicine (RR = 1.37; P < .001). In addition, CG did not increase the incidence of adverse events for vitiligo (RR = 0.79; P = .05). CG as a complementary medicine has a potential benefit in treatment of vitiligo. However, since the methodological flaws in the studies we included, more high-quality randomized controlled trials are warranted.

Supramolecular nanovesicles with in-situ switchable photothermal/photodynamic effects for precisely controllable cancer phototherapy

The combination of photodynamic therapy (PDT) and photothermal therapy (PTT) can significantly enhance antitumor efficacy via a synergistic therapeutic effect. However, developing a controllable and effective strategy for combined phototherapy remains a challenge. Herein, an intelligent photoactive agent based on supramolecular nanovesicles is presented, with a capacity of glutathione-responsive transformation from PTT to PDT to achieve controllable phototherapy. When linked by cystamine, the self-assembling nature of hydrophobic corrole molecules and hydrophilic PEG5000 chains induces the formation of supramolecular nanovesicles, which exhibit a high photothermal conversion efficiency of 55.1% due to the strong π-stacking of photosensitizing corrole molecules, while the fluorescence and photodynamic effect are inhibited. Interestingly, upon exposure to glutathione, the disulfide bonds of cystamine would gradually dissociate, resulting in the disassembly of nanovesicles into discrete corrole molecules and the concomitant recovery of photodynamic ability. In vitro and in vivo studies demonstrated that the tumor-responsive structural change of supramolecular nanovesicles and PTT-to-PDT transformation were crucial for optimized antitumor outcomes, allowing PTT, combined PTT/PDT, and PDT at different time points after one injection. Our work manifested that supramolecular photoactive nanovesicles could be rationally designed to realize controllable phototherapy, providing a unique strategy for constructing intelligent nanomedicine.

Recent Advances of Tumor Microenvironment-Responsive Nanomedicines-Energized Combined Phototherapy of Cancers.

Photodynamic therapy (PDT) has emerged as a powerful tumor treatment tool due to its advantages including minimal invasiveness, high selectivity and thus dampened side effects. On the other side, the efficacy of PDT is severely frustrated by the limited oxygen level in tumors, thus promoting its combination with other therapies, particularly photothermal therapy (PTT) for bolstered tumor treatment outcomes. Meanwhile, nanomedicines that could respond to various stimuli in the tumor microenvironment (TME) provide tremendous benefits for combined phototherapy with efficient hypoxia relief, tailorable drug release and activation, improved cellular uptake and intratumoral penetration of nanocarriers, etc. In this review, we will introduce the merits of combining PTT with PDT, summarize the recent important progress of combined phototherapies and their combinations with the dominant tumor treatment regimen, chemotherapy based on smart nanomedicines sensitive to various TME stimuli with a focus on their sophisticated designs, and discuss the challenges and future developments of nanomedicine-mediated combined phototherapies.

Mycosis Fungoides

Mycosis fungoides, also known as cutaneous T-Cell lymphoma, is a rare hematologic malignancy characterized by cutaneous involvement. There is significant variability in dermatologic presentation in early stages and often atypical pathology findings on biopsy that often make early diagnosis quite challenging. Here we present a case of an elderly patient who presented with chronic pruritis and cutaneous T-Cell Lymphoma involving the entire body, currently managed with a combination of phototherapy and anti-pruritic topical medications.

Mannan-functionalized black phosphorus nanosheets mediate the targeted elimination of intracellular bacteria via combined phototherapy

Mannan-functionalized black phosphorus nanosheets mediate the targeted elimination of intracellular bacteria via combined phototherapy

Platelet-mimetic nano-sensor for combating postoperative recurrence and wound infection of triple-negative breast cancer

Tumor recurrence mainly triggered by tumor residual cells significantly contributes to mortality following breast tumor resection, and meanwhile post-surgical bacterial wound infections may accelerate tumor recurrence due to a series of infection-related complications. In this study, a nano-sensor system, Van-ICG@PLT, is constructed by a membrane camouflage and small molecule drug self-assembly strategy. This nano-sensor harnesses the innate tropism of platelets (PLT) to deliver vancomycin (Van) and indocyanine green (ICG) to surgical incisions, effectively eliminating both residual tumor cells and bacterial infections. Our findings demonstrate that Van-ICG@PLT preferentially accumulates at surgical wound. Under near-infrared (NIR) laser irradiation, Van-ICG@PLT exhibits significant cytotoxicity against 4T1 cells. Additionally, it is found to significantly promote ROS production thus inhibiting Staphylococcus aureus (S. aureus) growth, underscoring the synergistic benefits of phototherapy in combination with antibiotic treatment. In the 4T1 post-surgery recurrence mice model, Van-ICG@PLT is shown to efficiently ablate tumors in tumor-bearing mice (tumor inhibition rate of about 83%), and it demonstrates an excellent anti-infective effect in mice abscess models. Taken together, Van-ICG@PLT represents a promising paradigm in post-surgical adjuvant therapy (PAT). Its dual benefit in inhibiting cancer growth and promoting antibacterial activity makes Van-ICG@PLT a valuable addition to the existing arsenal of therapeutic options available for breast cancer patients.

Dual Stimuli-Responsive Micelles for Imaging-Guided Mitochondrion-Targeted Photothermal/Photodynamic/Chemo Combination Therapy-Induced Immunogenic Cell Death.

As the special modality of cell death, immunogenic cell death (ICD) could activate immune response. Phototherapy in combination with chemotherapy (CT) is a particularly efficient tumor ICD inducing method that could overcome the defects of monotherapies. In this study, new dual stimuli-responsive micelles were designed and prepared for imaging-guided mitochondrion-targeted photothermal/photodynamic/CT combination therapy through inducing ICD. A dual-sensitive methoxy-polyethylene glycol-SS-poly(L-γ-glutamylglutamine)-SS-IR780 (mPEG-SS-PGG-SS-IR780) polymer was synthesized by grafting IR780 with biodegradable di-carboxyl PGG as the backbone, and mPEG-SS-PGG-SS-IR780/paclitaxel micelles (mPEG-SS-PGG-SS-IR780/PTXL MCs) were synthesized by encapsulating PTXL in the hydrophobic core. In-vivo and -vitro results demonstrated that the three-mode combination micelles inhibited tumor growth and enhanced the therapeutic efficacy of immunotherapy. The dual stimuli-responsive mPEG-SS-PGG-SS-IR780/PTXL MCs were able to facilitate tumor cell endocytosis of nanoparticles. They were also capable of promoting micelles disintegration and accelerating PTXL release. The mPEG-SS-PGG-SS-IR780/PTXL MCs induced mitochondrial dysfunction by directly targeting the mitochondria, considering the thermo- and reactive oxygen species (ROS) sensitivity of the mitochondria. Furthermore, the mPEG-SS-PGG-SS-IR780/PTXL MCs could play the diagnostic and therapeutic roles via imaging capabilities. In summary, this study formulated a high-efficiency nanoscale platform with great potential in combined therapy for tumors through ICD.

Dual-targeted delivery of paclitaxel and indocyanine green with aptamer-modified ferritin for synergetic chemo-phototherapy

The combination of phototherapy and chemotherapy has become attractive and effective cancer treatment. However, the accurate delivery of both chemo-phototherapy drugs to the target site as well as the development of high-efficient phototherapy and chemotherapy drugs remain major challenges. In this study, indocyanine green (ICG) and paclitaxel (PTX)-loaded aptamer ferritin (HAS1411-PTX-ICG) was developed as a biocompatible nanoplatform for combined chemo/photothermal/photodynamic (PTT/PDT) therapy that was safe and highly effective against tumors. HAS1411 was prepared by coupling aptamer AS1411 to the surface of human H chain ferritin (HFtn) by the carbon diimide method to further enhance the targeting of HFtn. Both ICG and PTX were effectively encapsulated in the HAS1411 by incubation at 60 ℃. Moreover, under near-infrared (NIR) light irradiation, HAS1411 enhanced the photothermal effect and cell internalization of ICG, as well as the production of reactive oxygen species in cancer cells. HAS1411-PTX-ICG displayed effective cytotoxicity and a significant tumor spheroids inhibitory effect owning to the improved internalization of PTX and ICG mediated by TfR1 and nucleolin dual receptors. Co-loaded PTX combined with ICG can produce chemo/PTT/PDT under near-infrared (NIR) light irradiation, enhancing the anti-tumor effect. The dual-targeting HAS1411 nanocarrier developed in this study can be a promising delivery system for cancer therapy and the fabricated HAS1411-PTX-ICG possesses potential application in chemo-phototherapy.

Controllable Regulation of Ag2 S Quantum Dots-Mediated Protein Nanoassemblies for Imaging-Guided Synergistic PDT/PTT/Chemotherapy Against Hypoxic Tumor.

The combination of phototherapy and chemotherapy holds great potential for cancer treatment, while hypoxia in tumor as well as unexpected drug release largely restrict anticancer therapy. Inspired by the natural intelligence, herein we present for the first time a "bottom-up" protein self-assembly strategy mediated by NIR quantum dots (QDs) with multicharged electrostatic interactions to develop a tumor microenvironment (TME)-responsive theranostic nanoplatform for imaging-guided synergistic PDT/PTT/chemotherapy. Catalase (CAT) possesses diverse surface charge distribution under different pH conditions. After modification by Ce6, the formulated CAT-Ce6 with patchy negative charges can be assembled with NIR Ag2 S QDs by regulating their electrostatic interactions, allowing for effective incorporation of specific anticancer drug oxaliplatin (Oxa). Such Ag2 S@CAT-Ce6@Oxa nanosystems are able to visualize nanoparticle accumulation to guide the subsequent phototherapy, together with significant alleviation of tumor hypoxia to further enhance PDT. Moreover, the acidic TME triggers controllable disassembly through weakening the CAT surface charge to disrupt electrostatic interactions in assemblies, allowing for sustained drug release. Both in vitro and in vivo results demonstrate remarkable inhibition of colorectal tumor growth with a synergistic effect. Overall, this multicharged electrostatic protein self-assembly strategy provides a versatile platform for realizing TME-specific theranostics with high efficiency and safety, promising for clinical translation. This article is protected by copyright. All rights reserved.