Figure 2. (a) pH-responsive EtNBSS fabricated from phenothiazinium dye and their antibacterial ability activated by acid. (b) Efficient MPTT bacterial killing and biofilm eradication achieved by pH-responsive EtNBSS under ultralow laser dose delivery. (c) Efficient MPTT treatment of drug resistant bacterial keratitis and endophthalmitis in vivo. Hydrolysis profiles of (d) EtNBSS and (e) EtNBSC under different pH conditions at 37 °C determined from HPLC results. (f) Representative SEM images of bacteria after photoirradiation with or without a 650 nm laser (0.2 W/cm2, 3 min). Reproduced from Ref. [108] with permission. Copyright 2022 American Chemical Society.
3.1.3. Semiconductor polymer NPs (SPNs)
SPNs is a series of π-conjugated polymer that can efficiently convert NIR light into heat. SPNs has good biocompatibility and size-independent optical properties, which makes it different from most semiconductor inorganic NPs. SPNs has attracted a lot of attention in the biomedical field. SPNS often have excellent optical stability and can be designed to display adjustable optical properties through simple molecular engineering.[109-112] SPNs also have the advantages of bioinert, large absorption cross section, high PCE, and has been widely used in fluorescence and photoacoustic imaging (PAI),[113-115] PTT and PDT and other fields. SPNS with photothermal properties can be used directly as photomedicine or as light sensors that can activate heat-sensitive therapeutic drugs. Develop heat-activated SPN-based therapeutics by loading or conjugated SPNs with therapeutic agents (e.g., agonists, genes, and enzymes) to amplify the therapeutic effect.
Polydopamine (PDA) has garnered significant research attention due to its favorable biocompatibility and efficient photothermal conversion properties. The PCE of PDA NPs can reach an impressive 40%. Furthermore, PDA can readily engage with diverse functional molecules, including proteins and polysaccharides, through mechanisms like Michael addition and Schiff base reactions.[116-118] This enables effective surface functionalization of PDA materials. In a study by Fan et al., PDA NPs were developed to enhance the specificity and efficacy of bacterial targeting and eradication at relatively low temperatures. The choice of PDA stemmed from its remarkable photothermal conversion capability. To augment the bacterial interaction, the surface of the NPs was modified using Magainin I (MagI), an antimicrobial peptide with specific affinity for bacteria. MagI-PEG@PDA NPs effectively eradicated E. coli at a moderate temperature of approximately 45 °C when exposed to NIR light.[119] These findings could propel practical clinical applications of MPTT, offering new avenues for combating bacterial infections. Ding et al. developed a PDA-coated nucleic acid nanogel as a therapeutic construct for siRNA-mediated MPTT. In this approach, siRNAs targeting the HSP70 play the role of crosslinkers, guiding the assembly of DNA-grafted polycaprolactone (DNA-g-PCL) into nanoscale hydrogel via nucleic acid hybridization. Subsequently, the resulting siRNA-embedded nanogels were enveloped with a thin layer of PDA to safeguard the nanogels from enzymatic degradation and confer upon them exceptional photothermal conversion capabilities when exposed to NIR light. By further incorporating surface PEGylation, this comprehensive siRNA delivery complex boasts a triple-layered protective shield. This intricate design demonstrated remarkable efficacy in selectively eradicating tumors under relatively mild conditions.[120] This work showcased the potential of harnessing nucleic acid nanogels in tandem with polydopamine coating for siRNA-guided MPTT, advancing the landscape of targeted and controlled therapeutic interventions. Li et al. devised a strategy involving functional conjugated polymer NPs (CPNs-G) to amplify MPTT effect. The elevated temperature augments the catalytic activity of glucose oxidase (GOx), thereby curbing ATP generation and suppressing the expression of HSPs.[121] Consequently, this study introduces an innovative approach to surmount thermoresistance by orchestrating an enzyme-mediated starvation effect, effectively modulated by NIR light. Ma et al. innovated a nanobomb concept by harnessing the self-assembly of a NIR-II aggregation-induced emission (AIE) polymer, PBPTV, in conjunction with a carbon monoxide (CO) carrier mPEG. This intelligent nanobomb demonstrated the capacity to detonate within the tumor microenvironment (TME) characterized by elevated levels of hydrogen peroxide. Upon detonation, the nanobomb releases CO directly into cancer cells, leading to a substantial suppression of HSP expression (Figure 3).[122] Consequently, this intervention significantly enhances the efficacy of MPTT by ameliorating the antitumor effect.