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.