Multifunctional photothermal hydrogels: Design principles, various functions, and promising biological applications

Photothermal hydrogels with excellent photo responsive and thermal conversion ability had attract a great deal of attention from researchers to explore their biological applications.This review aimed to provide a comprehensive overview of photothermal hydrogels,focusing on their design principles,various functions,and biological applications.Firstly,several classifications of photothermal hydrogels were given according to different photothermal agents(metal,metal sulfide/oxide,MXene,carbon-based,dyes,black phosphorus,and polymer)utilized in hydrogel construction.The photothermal conversion mechanism and hydrogel fabrication were also discussed in detail.Then,the relationship between their photothermal conversion property and functions,together with some indispensable property such as biocompatibility,adhesion,mechanical properties,and self-healing properties was fully introduced.Furthermore,the ap-plications of photothermal hydrogels in the biomedical(i.e.,wound healing,antibacterial treatments,con-trolled drug release,bone repair,and tumor treatment)was summarized.Finally,the future opportunities and challenges of photothermal hydrogels were proposed.We believe that this review could provide a new horizon for further preparation of photothermal hydrogels,and could promote their applications in widerfields.

Largeπ-extended donor-acceptor polymers for highly efficient in vivo near-infrared photoacoustic imaging and photothermal tumor therapy

Semiconducting polymers(SPs)with intensive near-infrared(NIR)absorption and high photothermal conversion efficiencies have been employed as a new generation of photothermal agents(PTAs)for“all-in-one”theranostic nanoplatforms with integrated photoacoustic imaging(PAI)and photothermal therapy(PTT)functions.However,the lack of facile molecular design principles impedes the development of highly efficient NIR PTAs.Herein,a facile molecular design strategy based on largeπ-extended donor-acceptor(L-π-D-A)structure is reported for achieving SPs(SP1-SP3)with highly efficient in vitro and in vivo PAI and PTT capabilities.Through adjusting the conjugation length and planarity of the donor units,both SP3 and corresponding nanoparticle(SPN)SPN3 exhibit stronger D-A strength,intensive NIR absorption,enhanced absorption coefficient,and higher photothermal conversion efficiency(up to 61.8%).The excellent photothermal conversion efficiencies make SPN1-SPN3 produce efficient inhibition of tumor growth with excellent biocompatibility and prominent PAI performance with a high contrast manner in living mice at a low systemic injection mass.Our research highlights that the new L-π-D-A molecular design is an effective strategy to obtain highly efficient polymeric NIR PTAs for high desirable cancer phototheranostic nanoplatforms.

An endoplasmic reticulum-targeted organic photothermal agent for enhanced cancer therapy

Developing selectively targeted photothermal agents to reduce side effects in photothermal therapy remains a great challenge. Inspired by the key role of endoplasmic reticulum in the protein synthesis and intracellular signal transduction, particularly for the immunogenic cell death induced by endoplasmic reticulum stress, we developed an endoplasmic reticulum-targeted organic photothermal agent(Ts-PTRGD) for enhancing photothermal therapy of tumor. The photothermal agent was covalently attached with 4-methylbenzenesulfonamide and cyclic Arg-Gly-Asp(c RGD) peptide for realizing the targeting of endoplasmic reticulum and tumor cell. Owing to its amphiphilic properties, it readily self-assembles in water to form nanoparticles. The photothermal agent possesses excellent photophysical properties and biological compatibility. In vitro and in vivo experiments demonstrate that it can actively target endoplasmic reticulum and effectively ablate tumor with near-infrared laser.

Strategies for efficient photothermal therapy at mild temperatures:Progresses and challenges

Photothermal therapy(PTT), typically ablates tumors via hyperthermia generated from photothermal agents(PTAs) under laser irradiation, has attracted great attentions in the past decades. Unfortunately,longstanding, frequent and high-power density laser irradiations are needed to maintain the hyperthermal status(>50 ℃) for efficient therapy, which will damage the skin and nearby healthy tissues. Suppressing cancer cells with a mild temperature elevation is more attractive and feasible for PTT. Recently,low-temperature photothermal therapy(LTPTT), which could inhibit tumor under mild hyperthermia, has been widely investigated by researchers. Herein, we systematically summarized the strategies to achieve LTPTT. Diverse PTAs including organic and inorganic materials reported for LTPTT were introduced. The established strategies for LTPTT were intensively described. Finally, the challenges as well as future perspectives in this field were discussed.

Hydrophilic bismuth sulfur nanoflower superstructures with an improved photothermal efficiency for ablation of cancer cells

Nanomaterials with intense near-infrared （NIR） absorption exhibit effective photon-to-thermal energy transfer capabilities and can generate heat to ablate cancer cells, thus playing a pivotal role in photothermal cancer therapeutics. Herein, hydrophilic flower-like bismuth sulfur （Bi2S3） superstructures with uniform size and improved NIR absorption were controllably synthesized via a facile solvothermal procedure assisted by polyvinylpyrrolidone （PVP）, which could adjust the product morphology. Induced by an 808-nm laser, the as-prepared Bi2S3 nanoflowers exhibited much higher photothermal conversion efficiency （64.3%） than that of Bi2S3 nanobelts （36.5%） prepared in the absence of PVP. This can be attributed not only to the Bi2S3 nanoflower superstructures assembled by 3-dimensional crumpled-paper-like nanosheets serving as many laser-cavity mirrors with improved reflectivity and absorption of NIR light but also to the amorphous structures with a lower band gap. Thus, to achieve the same temperature increase, the concentration or laser power density could be greatly reduced when using Bi2S3 nanoflowers compared to when using Bi2S3 nanobelts, which makes them more favorable for use in therapy due to decreased toxicity. Furthermore, these Bi2S3 nanoflowers effectively achieved photothermal ablation of cancer ceils in vitro and in vivo. These results not only supported the Bi2S3 nanoflowers as a promising photothermal agent for cancer therapy but also paved an approach to exploit new agents with improved photothermal efficiency.

Photothermal performance of MFe2O4 nanoparticles

Photothermal therapy(PTT) has emerged as one of the promising cancer therapy approaches.As a representative photothermal agent(PTA),magnetite possesses many advantages such as biodegradability and biocompatibility.However,photothermal instability hampers its further application.Herein,we systematically synthesized three kinds of ferrite nanoparticles and detailedly investigated their photothermal effect.Compared with Fe304 and MnFe2 O4 nanoparticles,ZnFe2 O4 nanoparticles exhibited a superior photothermal effect.After preservation for 70 days,the photothermal effect of Fe304 and MnFe2 O4 nanoparticles observably declined while ZnFe2 O4 nanoparticles showed slight decrease.Furthermore,in vitro experiment,ZnFe2 O4 nanoparticles showed little toxicity to cells and achieved outstanding effect in killing cancer cells under NIR laser irradiation.Overall,through synthesizing and studying three kinds of ferrite MFe2 O4 nanoparticles,we obtained ferrites as PTAs and learned about their changing trend in photothermal effect,expecting it can inspire further exploration of photothermal agents.

Photo-Activated Ferroptosis for Cancer Therapy: Advances, Challenges, and Prospects

Ferroptosis, a recently identified form of non-apoptotic programmed cell death, has attracted significant attention in the field of cancer therapy due to its unique mechanism of cell death. To meet the demands of ferroptosis-mediated cancer treatment, several small molecule-based drugs have been reported for the implementation of ferroptosis. However, some cancer cells are inherently resistant to these drugs, and the lack of selectivity of these drugs against cancer cells can limit their clinical application. Recent advancements in light-mediated biomedical techniques offer a promising alternative for the development of ferroptotic therapy, that is photo-controlled activation of ferroptosis. In this review, we systematically summarize the current strategies for photo-controlled ferroptosis activation and detail analysis of the underlying mechanisms of those photo-controlled ferroptotic therapies. Finally, we discuss the challenges associated with photo-activated ferroptosis and provide an outlook on the future developments in ferroptotic cancer therapy.

Selective inactivation of Gram-positive bacteria in vitro and in vivo through metabolic labelling

Bacterial infections are grave threats to human health,particularly those caused by the most common Grampositive bacteria.The massive administration of broad-spectrum antibiotics to treat various bacterial infections has led to the evolution and spread of drug resistance.As a universal antimicrobial technique unapt to induce drug resistance,photothermal therapy(PTT)is attracting extensive attention in recent years.However,its unspecific killing capability and side effects towards adjacent mammalian cells severely impede the practical applications.Herein,we proposed a metabolic engineering strategy to selectively inactivate Gram-positive bacteria by PTT.A bioorthogonal photothermal agent was prepared by the conjugation of IR-780 iodide and dibenzocyclooctyne(IR780-DBCO).Upon pre-metabolizing with 3-azido-D-alanine,Gram-positive bacteria rather than Gramnegative ones,such as Staphylococcus aureus and vancomycinresistant Enterococcus faecalis(VRE),could be specifically tied up by the explosive IR780-DBCO via copper-free click chemistry.Thereafter,they spontaneously detonated under 15 min near-infrared light irradiation and inactivated nearly 100% Gram-positive bacteria in vitro.Moreover,superbug VRE-induced infection was significantly inhibited by this approach in a mouse skin wound model.This metabolic labelling-based photothermal ablation strategy specific to Gram-positive microbes would stimulate the development of precise antibacterial candidates for preclinical applications.