Photosensitizing Drug Research Articles

Singlet Oxygen in Photodynamic Therapy.

Photodynamic therapy (PDT) is a therapeutic modality that depends on the interaction of light, photosensitizers, and oxygen. The photon absorption and energy transfer process can lead to the Type II photochemical reaction of the photosensitizer and the production of singlet oxygen (1O2), which strongly oxidizes and reacts with biomolecules, ultimately causing oxidative damage to the target cells. Therefore, 1O2 is regarded as the key photocytotoxic species accountable for the initial photodynamic reactions for Type II photosensitizers. This article will provide a comprehensive review of 1O2 properties, 1O2 production, and 1O2 detection in the PDT process. The available 1O2 data of regulatory-approved photosensitizing drugs will also be discussed.

Synthesis and evaluation of new tetrapyrrole derivatives with photodynamic anti-tumor effects

As a promising anti-tumor method, photodynamic therapy (PDT) has garnered increased interest over the past decades. Since the efficacy of PDT relies on the properties of photosensitizers, tremendous efforts have been exerted in the quest for novel photoactive agents with long wavelength absorbance and high phototoxicity. In this investigation, a series of five tetrapyrrole derivatives were newly synthesized and evaluated. They all manifested sharp UV–vis absorption peak at ∼680 nm, high molar extinction coefficient (>74200 L mol−1 cm−1), impressive reactive oxygen species generation abilities and obvious photo-damage on cancer in vitro and in vivo. Among them, I4 displayed the most excellent singlet oxygen generation slope (K = 0.0531 s−1, ΦΔ = 0.87), the strongest anti-proliferation effects towards human esophageal cancer cell line Eca-109 in vitro, and more remarkable tumor inhibition rates (90.2 %) than m-THPC in vivo. Subcellular localization experiments demonstrated that I4 could distribute in mitochondria, endoplasmic reticulum and lysosomes. Hence, compound I4 could be viewed as a potential photosensitizer drug for further studies in PDT.

Voltage-Gated Ion Channels: Structure, Pharmacology and Photopharmacology.

Voltage-gated ion channels are transmembrane proteins responsible for the generation and propagation of action potentials in excitable cells. Over the last decade, advancements have enabled the elucidation of crystal structures of ion channels. This progress in structural understanding, particularly in identifying the binding sites of local anesthetics, opens avenues for the design of novel compounds capable of modulating ion conduction. However, many traditional drugs lack selectivity and come with adverse side effects. The emergence of photopharmacology has provided an orthogonal way of controlling the activity of compounds, enabling the regulation of ion conduction with light. In this review, we explore the central pore region of voltage-gated sodium and potassium channels, providing insights from both structural and pharmacological perspectives. We discuss the different binding modes of synthetic compounds that can physically occlude the pore and, therefore, block ion conduction. Moreover, we examine recent advances in the photopharmacology of voltage-gated ion channels, introducing molecular approaches aimed at controlling their activity by using photosensitive drugs.

DNA aptamer-empowered self-assembly full-API nanodrug for enhanced photodynamic and chemotherapy synergistic cancer therapy

Nanomedicine holds promising potential for cancer therapy, yet challenges such as low active pharmaceutical ingredient (API), nanocarrier toxicity, complex preparation processes, and a lack of targeting ability hinder clinical applications. Here, we present a versatile method for preparing DNA aptamer-based full-API nanodrugs (ICS AFANDs). This approach involves the self-assembly of FDA-approved chemotherapeutics (irinotecan), photosensitive drugs (Chlorin e6, Ce6), and the DNA molecule of the Sgc8 aptamer. DNA aptamers are firstly confirmed to not only impart solubilization and targeting ability to ICS AFANDs but also play a pivotal role in engineering and stabilizing the formation of self-assembled nanodrugs. Our method not only significantly enhances the chemotherapy effectiveness of irinotecan by 102-fold, but also improves the near-infrared (NIR) fluorescence properties and photoactivity of Ce6. Combining photodynamic therapy (PDT) and chemotherapy (CT), our ICS AFANDs achieve complete suppression of colorectal cancer growth, with only one dose and one laser treatment, all without apparent side effects. Our strategy is a versatile method for preparing carrier-free and multifunctional DNA nanodrugs for synergistic tumor therapy. The smart and efficient full-API DNA nanodrug not only broadens the scope of synergistic tumor therapy but also facilitates the practical translation of DNA nanodrugs to clinical use.

Unraveling the effect of molecular medium on the fluorosolvatochromism of the biphenyl- salicylate derivative drug Diflunisal: Experimental and computational study

Understanding the photochemical behavior of a photosensitive drug through its molecular properties is crucial for assessing potential phototoxicity. In this study, we examine how the molecular microenvironment influences the physicochemical and photochemical properties of Diflunisal (DIF), an organofluorine salicylate derivative drug. To elucidate the photophysical properties of DIF, we employed absorption and fluorescence spectroscopy techniques combined with various DFT-based computational methods. The solvatochromic and fluorescence behaviors of DIF were investigated employing various neat solvents of various polarity and hydrogen bonding (HB) capabilities. The molecular behavior of DIF exhibited mixed fluorosolvatochromism, where a negative fluorosolvatochromism is noted as solvent polarity increases, where DIF exhibited positive fluorosolvatochromism within the examined set of protic polar solvents. These fluorosolvatochromic behaviors suggest that a combination of factors, including solvent polarity, hydrogen bonding capacity, and specific solvation effects, influences the fluorosolvatochromic properties of DIF. To elucidate the impact of specific and non-specific interactions between DIF and solvent on the fluorosolvatochromism of DIF, we utilized Catalán’s four empirical scales model. The results revealed that the solvent’s acidity, basicity, and polarizability had approximately equivalent and notable impacts on the fluorosolvatochromic behavior of DIF. For a molecular-level explanation of the experimental spectral properties, we employed DFT and TD-DFT/B3LYP/6–31 + G(d) computational methods, incorporating the IEFPCM implicit solvation approach. It is also revealed that the negative fluorosolvatochromism of DIF is attributed to the solvent’s impact on the main electronic transition, namely HOMO → LUMO. It is revealed as well that not only the salicylate moiety is affected by the solvent, but also the biphenyl moiety can exhibit a major contribution to the observed behavior. The results presented here offer insights into the photochemical behavior of DIF within various microenvironments at the molecular level. This understanding could inform future endeavors aimed at mitigating induced toxicity and side effects of DIF.

Phase 1 study to evaluate safety and preliminary efficacy of padeliporfin vascular targeted photodynamic therapy (VTP) in patients with locally advanced (LA) unresectable pancreatic ductal adenocarcinoma (PDAC).

TPS4204 Background: Pancreatic cancer is the third most common cause of cancer death. Surgery offers the best survival rates however only a minority of patients are eligible. Approximately 15-20% of patients are deemed unresectable due to vascular involvement LA. Conversion of unresectable tumors, due to vascular involvement to resectable, is an unmet clinical need. Methods: A novel approach was developed to destroy the tumor encasing the artery combining padeliporfin, a photosensitive drug, locally activated by laser light illumination. The effectiveness of the strategy was confirmed in an orthotopic mouse model. A proof-of-concept study using 12 non-tumor pigs demonstrated an acceptable safety profile. A phase I dose escalation trial (NCT5918783) will be performed to evaluate the safety and maximal tolerated dose (MTD) of laser light dose of padeliporfin VTP. VTP will be delivered through an endovascular fiber integrated in a standard angioplasty balloon. The balloon will be advanced under fluoroscopy to the encased vascular segment of the superior mesenteric artery (SMA) and inflated. Following IV administration of padeliporfin, it will be activated by the laser light. Part A will be a classic 3+3 dose-escalation design to determine the MTD of laser light. The identified MTD will be applied in the Part B for preliminary efficacy evaluation. The primary objectives are to determine safety and MTD and/or recommended phase 2 laser light dose of VTP treatment. Secondary objectives are: rate of surgical conversion; evaluation of the pattern of disease progression (local regional and/or metastatic disease) after VTP based on CT. Standard of care surgery can be performed after 14 days post VTP. Key inclusion criteria: patients with histologically/cytologically confirmed stage III unresectable LA-PDAC in the head/uncinate process of the pancreas, with SMA solid tumor contact ˃180° with measurable disease per RECIST 1.1 and ECOG 0-1. Key exclusion criteria: metastatic disease, other malignancy, photosensitive skin diseases or porphyria, concurrent investigational therapy within past 30 days, medically uncontrolled moderate or severe ascites, previous radiation to pancreas, SMA variants. Recruitment begins in April 2024. Conversion of unresectable locally advanced pancreatic cancer to surgery is a critical unmet need. This phase I trial explores a novel approach to treat the tumor encasement enabling surgery. Clinical trial information: NCT5918783 .

Characterization and efficacy of C60 nano-photosensitive drugs in colorectal cancer treatment

BackgroundFullerenes C60 shows great potential for drug transport. C60 generates large amounts of singlet oxygen upon photoexcitation, which has a significant inhibitory effect on tumor cells, so the photosensitive properties of C60 were exploited for photodynamic therapy of tumors by laser irradiation. MethodsIn this study, C60-NH2 was functionalized by introducing amino acids on the surface of C60, coupled with 5-FU to obtain C60 amino acid-derived drugs (C60AF, C60GF, C60LF), and activated photosensitive drugs (C60AFL, C60GFL, C60LFL) were obtained by laser irradiation. The C60 nano-photosensitive drugs were characterized in various ways, and the efficacy and safety of C60 nano-photosensitive drugs were verified by cellular experiments and animal experiments. Bioinformatics methods and cellular experiments were used to confirm the photosensitive drug targets and verify the therapeutic targets with C60AF. ResultsPhotosensitised tumor-targeted drug delivery effectively crosses cell membranes, leads to more apoptotic cell death, and provides higher anti-tumor efficacy and safety in vitro and in vivo colorectal cancer pharmacodynamic assays compared to free 5-FU.C60 photosensitized drug promotes tumor killing by inhibiting the colorectal cancer FLOR1 tumor protein target, with no significant toxic effects on normal organs. ConclusionC60 photosensitized drug delivery systems are expected to improve efficacy and reduce side effects in the future treatment of colorectal cancer. Further and better development and design of drugs and vectors for colorectal cancer therapy.

Sodium copper chlorophyllin conjugated with Ag plasmonic nanoparticles as efficient nanostructure for application in photodynamic therapy

Photodynamic therapy (PDT) is a method that uses light-sensitive photosensitizers to stimulate cells with specific wavelengths. Nanoparticles (NPs) are an emerging technology in PDT, offering advantages over classical photosensitizers. The amalgamation of silver NPs and photosensitizer drugs has gained significant attention in PDT. We conjugated Ag NPs to sodium-copper chlorophyllin (SCC) in this research. The binding of Ag NPs to SCC was examined using X-ray diffraction, SEM, EDS, DLS, Zeta potential, and FTIR analyses. The optical properties of SCC before and after binding toAg NPs were performed through Photoluminescence (PL) analysis and UV–visible spectroscopy, as well as the production of reactive oxygen species (ROS) and free radicals (hydroxyl radical) before and after binding through the photobleaching phenomenon of methylene blue and photochemical degradation of anthracene. SCC exhibits high absorption in the visible spectrum violet-blue (350–470 nm) and red (570–710 nm) regions. HeLa cells and red LED were used to investigate the cytotoxicity (MTT assay) of SCC attached to Ag NPs.

Preventing Photosensitive Drugs from Degradation.

Preventing Photosensitive Drugs from Degradation.

Photosensitizing Herbs as Potential Therapeutics: A Prospective Insights into their Mechanisms for the Development of Novel Drug Leads in War with Cancer and Other Human Diseases

In recent years, photodynamic therapy (PDT) has been accepted as an alternative option for the treatment of a wide spectrum of human ailments. It is a minimally invasive treatment that involves the interaction of a non-toxic photosensitizer. In PDT, combining photosensitizing (PS) agent that absorbs specified wavelength of light, which in turn produces free radical molecules to eliminate unwanted cells and tissues. The photosensitization process is activated by the light-induced excitation of molecules within the tissue. Bioactive principles acquired from plants documented as nature-inspired potential photosensitizers with varied properties against microbes, insects, or tumor cells. PDT is a promising method for removing diverse types of cancers but needs to be recognized in therapy as conventional chemotherapy. At present, natural compounds with PS properties are being continuously unearthed and identified. As of now, hundreds of photosensitive drugs or drug leads identified from natural sources with reduced or no toxicity to healthy tissues and no side effects encourage investigators to pursue natural PS for PDT. Although existing PS was developed years back, only a handful of them are engaged in human clinical applications. The main classes of natural photosensitizers discussed in this review are chlorophylls (hypocrellin A and B), hypericin, chlorins (Chlorin e6), and other emerging ones such as curcumin. Hence, the present review aimed to explore the efficacious PS properties of a few herbal-derived PS, preferably the potential ones in terms of specificity, and mechanism of action, inducing less or no toxicity to normal cells but their other medicinal applications.

Polydopamine-Coated Liposomes for Methylene Blue Delivery in Anticancer Photodynamic Therapy: Effects in 2D and 3D Cellular Models.

Photodynamic therapy (PDT) is a therapeutic option for cancer, in which photosensitizer (PS) drugs, light, and molecular oxygen generate reactive oxygen species (ROS) and induce cell death. First- and second-generation PSs presented with problems that hindered their efficacy, including low solubility. Thus, second-generation PSs loaded into nanocarriers were produced to enhance their cellular uptake and therapeutic efficacy. Among other compounds investigated, the dye methylene blue (MB) showed potential as a PS, and its photodynamic activity in tumor cells was reported even in its nanocarrier-delivered form, including liposomes. Here, we prepared polydopamine (PDA)-coated liposomes and efficiently adsorbed MB onto their surface. lipoPDA@MB vesicles were first physico-chemically characterized and studies on their light stability and on the in vitro release of MB were performed. Photodynamic effects were then assessed on a panel of 2D- and 3D-cultured cancer cell lines, comparing the results with those obtained using free MB. lipoPDA@MB uptake, type of cell death induced, and ability to generate ROS were also investigated. Our results show that lipoPDA@MB possesses higher photodynamic potency compared to MB in both 2D and 3D cell models, probably thanks to its higher uptake, ROS production, and apoptotic cell death induction. Therefore, lipoPDA@MB appears as an efficient drug delivery system for MB-based PDT.

A comprehensive study of prescribing, administering and drug handling medication errors in ten wards of a university hospital after implementation of electronic prescribing, clinical pharmacists or medication reconciliation.

Background and aim: Medication errors lead to preventable risks. Preventing strategies such as e-prescribing, clinical pharmacists and medication reconciliation have been implemented in recent years. However, information on long-term medication error rates in routine procedures is missing. Investigations: We aimed to identify predefined medication errors in ten wards of a university hospital where e-prescribing, clinical pharmacists and medication reconciliation have been partially implemented. Patient files were reviewed and routine processes were monitored for drug prescription errors (missing, unclear, outdated information), administration errors (wrong dispensed drugs) and drug handling errors (no light-, moisture-protection, wrong splitting, no separation of drugs, which ought to be taken by an empty stomach). Results: We analyzed 959 prescriptions with 933 solid peroral drugs for 182 patients (98 female, median age 66.5 years [Q25-Q75: 56-78 years]; the median number of drugs was 5 [Q25-Q75: 3-7]). The most frequent prescription error was a not specified drug form (91.1%). The most common administration error was a not adequately provided release dose formulation (72.7%). The lack of light protection for observed photosensitive drugs was the most frequent drug handling error (100%). We found a significantly higher amount of complete drug prescriptions with one of the implemented measurements e-prescribing, medication reconciliation and clinical pharmacists (Fisher's exact test two tailed, each p<0.001; CI 95%). Drug administration errors and drug handling errors were not significantly improved. Among the most frequently involved drug were drugs for acid-related disorders, immunosuppressant, and antineoplastic drugs. Conclusions: In the nearly 1,000 prescriptions and drugs analyzed, medication errors were still common. Various preventive strategies had been implemented in recent years, positively influencing the predefined errors rates.

Photo-triggered multifunctional gold-based hybrid nanoflowers promote infectious skin regeneration

The skin wound-healing under infectious conditions remains challenging owing to the lack of efficient strategies to inhibit drug-resistant bacteria growth and control inflammation. Photothermal therapy shows efficient antimicrobial effects, whereas it generates excessive heat to damage tissue and inflammation to impair tissue regeneration. Herein, we develop the multifunctional gold-based nanoflowers incorporated with photosensitizer (Ce6, for PDT) and anti-inflammatory drug (bromfenac sodium/BS). This allows for a nanosystem to combine the mild-photothermal therapy (mPTT), photodynamic therapy (PDT), and drug-controlled release anti-inflammation therapy for infectious skin regeneration. Upon laser irradiation, the local temperature increased (to a mild temperature of ∼ 45 ℃, mPTT) along with the singly linear oxygen (from PDT) for anti-infection; the release of BS was triggered for anti-inflammation. The multifunctional nanoflowers achieved 99 % antibacterial efficiencies and biofilm inhibition in vitro. They showed good biocompatibility and improved wound-healing in the animal models of subcutaneous abscess and skin wound infected with drug-resistant bacteria. In addition to the antibacterial effect from mPTT and PDT, the nanoflowers regulated the immune microenvironment by controlled releasing BS, inhibiting inflammation and promoting growth factor production, collagen deposition, and angiogenesis to improve skin wound-healing. Therefore, this study provides an advanced nano-system with photo-triggered antimicrobial and anti-inflammation activities, which improves infectious skin tissue regeneration.

Light‐assisted noncompetitive fluorescence immunoassay for photosensitive antibiotic detection

AbstractThe development of simple, sensitive, and efficient methods for antibiotic detection is of great significance for human health and environmental protection. Currently, although the competitive immunoassays are popular for detecting antibiotic molecules, they need to label antibiotic or specific antibody with signaling molecule. The development of noncompetitive immunoassay for antibiotic detection has always faced significant challenges. Herein, we have developed a light‐assisted noncompetitive immunoassay for the detection of antibiotics based on their photosensitive characteristic. Firstly, the antibody coated on the microplate specifically captures the target antibiotic. Afterward, under light irradiation, the captured photosensitive antibiotic produces reactive oxygen species (ROS), which oxidizes the added ROS dye to generate a fluorescent signal. Therefore, a noncompetitive immunoassay for antibiotic detection is achieved by utilizing the unique property of photosensitive antibiotics to generate ROS instead of labeling signaling molecules. By using antibiotics demeclocycline hydrochloride (DMCO) and polymyxin B (PMB) as research models, the proposed noncompetitive fluorescence immunoassay can specifically detect as low as 5 ng/mL DMCO and 70 ng/mL PMB, respectively. The light‐assisted noncompetitive immunoassay strategy opens a new avenue for simple, sensitive, label‐free, and high‐throughput detection of photosensitive antibiotics or photosensitive drugs.

Synthesis and photodynamic activity of novel thieno[3,2–b]thiophene fused BODIPYs with good bio-solubility and anti-aggregation effect

To discover new photosensitizers with long wavelength UV–visible absorption, high efficiency, and low side effects for photodynamic therapy, here, a series of novel thieno[3,2–b]thiophene-fused BODIPY derivatives were designed, synthesized and characterized. These compounds had a distinct absorption band at 640–680 nm, fluorescence emission at 650–760 nm, and good solubility with anti-aggregation effects. These new compounds possessed obvious singlet oxygen generation ability and photodynamic anti-Eca-109 cancer cells activities in vitro. Among them, compound II4 could be well uptaked by Eca-109 cells, and result in the apoptosis after laser irradiation, and have outstanding photodynamic efficiency both in vitro and in vivo. Therefore, II4 could be considered as a potential photosensitizer drug candidate for PDT and photo-imaging.

Recurrent Squamous Cell Carcinoma of the Upper Eyelid Treated With Combination Therapy of ALA Photodynamic Therapy and Surgery With Secondary Healing

Background. Cutaneous squamous cell carcinoma (cSCC) frequently occurs in photoexposed areas. Surgery remains the mainstay of treatment in attempts to reduce recurrence, but it must be combined with other therapy because of the limited excision possible in the region of the eyelid, lip, and nose. Photodynamic therapy (PDT) is a relatively new treatment modality that involves the administration of a photosensitizing drug and its subsequent activation by specific wavelengths of light to produce reactive oxygen species that specifically destroy target cells. Case Report. An 87-year-old female presented 4 weeks after initial resection with recurrent medium-differentiated cSCC measuring 5.2 cm × 3 cm × 2 cm in the left upper eyelid. Subsequent treatment involved palliative resection with an additional 1 cm at 3 margins of the tumor (excluding the bottom edge of the double eyelid line) and 3 applications of PDT using 5-aminolevulinic acid as the photosynthesizing agent in the open wound over a 2-week period. The wound healed well within 6 weeks. During the following 4 years, the patient showed satisfactory progress in both aesthetics and function, with no sign of recurrence or metastasis. Conclusion. Refractory cSCC was successfully managed using a combination of PDT and secondary healing, and functions of the head and face were well protected. These results suggest that such management warrants consideration in clinical settings.

Synthesis and evaluation of novel meso-substitutedphenyl dithieno[3,2-b]thiophene-fused BODIPY derivatives as efficient photosensitizers for photodynamic therapy

The discovery of new photosensitizer drugs with long wavelength Uv–vis absorption, high efficiency and low side-effects is still a challenge in photodynamic therapy. Here a series of novel meso-substitutedphenyl thieno[3,2-b]thiophene-fused BODIPY derivatives were designed, synthesized and characterized. All these compounds have strong absorption at 640–680 nm and obvious fluorescence emission at 650–760 nm. They exhibited high singlet oxygen generation ability and significant photodynamic efficiency against Eca-109 cancer cells. Compounds II4, II6, II9, II10 and II13 could generate intracellular ROS and induce cell apoptosis after laser irradiation, which displayed superior photodynamic efficiency against Eca-109 cells than Temoporfin in vitro and in vivo. Among them, compound II4 specifically exhibited excellent anti-tumor efficacy, and could be selected as a new drug candidate for PDT.

Manganese Dioxide/Gold-based Active Tumor Targeting Nanoprobes for Enhancing Photodynamic and Low-Temperature-Photothermal Combination Therapy in Lung Cancer.

Tumor drug resistance caused by the tumor microenvironment is an extremely difficult problem for researchers to solve. Nanoplatforms that integrate diagnosis and treatment have great advantages in tumor treatment, but the design and synthesis of simple and efficient nanoplatforms still face tremendous challenges. In this study, a novel Mn/Au@ir820/GA-CD133 nanoprobe was developed. The manganese dioxide/gold particles were prepared by coprecipitation/assembly, chemically coupled with CD133 antibody, and finally loaded with the photosensitive drug IR820 and the heat shock protein inhibitor Ganetespib. The nanoprobe demonstrated good tumor-targeting ability, increased the level of singlet oxygen produced from laser irradiation by effectively alleviating tumor hypoxia, and decreased the threshold of heat tolerance by downregulating the expression of HSP90 in tumor tissues. This nanoprobe successfully inhibited the growth and progression of tumor tissues in a tumor-bearing mouse model by improving the effectiveness of photodynamic and low-temperature photothermal combination therapy.

Solvent impact on the photochemical properties of anticancer drug PLX4720; a computational study

The advancement in pharmaceutical research has led to a successful era but limitations because of the drug's photochemical behavior triggered the researchers to explore the promising revolution. In terms of molecular properties rationalizing, the photosensitive drug photochemical response is essential for knowing the associated potential phototoxicity. It is the need of the hour to check the influence of the molecular microenvironment on photochemical and the physicochemical properties of the PLX4720 B-RAFV600E inhibitor. The geometry optimization was done with functional wB97XD. TD-DFT calculation has been performed to study the PLX4720 absorption spectra in different solvents and hydrogen bonding. The polarity-dependent spectral properties are indicative of the microenvironments that influenced the structural properties of PLX4720. In polar solvents, a notable enhancement is observed in the oscillation strength of HOMO → LUMO, the main electronic transition affects the photochemical properties of PLX4720. The charge delocalization is enhanced by these effects on the heteroatoms that comprise electron lone pairs. The inter-molecular hydrogen bonding among PLX4720 and the microenvironment study is also carried out. As a result, a substantial effect on the spectral properties of PLX4720 is reported. The physiochemical properties of PLX4720 complex are investigated using DMSO through hydrogen bonding interaction, NBO and DOS analyses. These results have exposed considerable changes in the structural properties of the PLX4720 which is an indication of the impact of intermolecular hydrogen bonding on photochemical properties. The results also reveal a notable charge density change in the selected atoms, leading to greater electronic transitions. The final results provided here give an insight into understanding about PLX4720 photochemical behavior at the molecular level in biologically mimicked microenvironments.

A hydrogel system for drug loading toward the synergistic application of reductive/heat-sensitive drugs

The preparation of hydrogels as drug carriers via radical-mediated polymerization has significant prospects, but the strong oxidizing ability of radicals and the high temperatures generated by the vigorous reactions limits the loading for reducing/heat-sensitive drugs. Herein, an applicable hydrogel synthesized by radical-mediated polymerization is reported for the loading and synergistic application of specific drugs. First, the desired sol is obtained by polymerizing functional monomers using a radical initiator, and then tannic-acid-assisted specific drug mediates sol-branched phenylboric acid group to form the required functional hydrogel (New-gel). Compared with the conventional single-step radical-mediated drug-loading hydrogel, the New-gel not only has better chemical/physical properties but also efficiently loads and releases drugs and maintains drug activity. Particularly, the New-gel has excellent loading capacity for oxygen, and exhibits significant practical therapeutic effects for diabetic wound repair. Furthermore, owing to its high light transmittance, the New-gel synergistically promotes the antibacterial effect of photosensitive drugs. This gelation strategy for loading drugs has further promising biomedical applications.