Figure 1. (a) Schematic illustration of the multifunctional theranostic
platform co-loaded with IR820, ZnCdSe/ZnS QDs and CQ for MPTT. (b) TEM
images of PIFC NPs. (c) UV–Vis spectra of CQ, PLGA NPs, IR820 and PIFC
NPs. (d) Heating and cooling curves of PIFC NPs and IR820 irradiated by
808 nm laser (1.0 W/cm2) over four ON/OFF cycles.
Reproduced from Ref. [94] with permission. Copyright 2022 Elsevier.
3.1.2. D-A structured small molecules
Donor–acceptor (D–A) structure is an effective means to regulate the
molecular energy band, which can reduce the oxidation potential and have
higher stability. So far, many D–A molecules have been reported, such
as benzothiadiazole, quinoxaline and their derivatives.[95-98] The
D–A structure can not only reduce the band gap of the molecule and
expand the absorption range of the molecule, but also explore the
influence of different functional groups on the properties of the
material. D–A structured small molecule fluorophores with properties
such as excellent biocompatibility, minimal cellular toxicity,
straightforward chemical modifiability, and favorable excretion
pharmacokinetics in biological systems are highly sought after for
potential clinical applications in NIR-II (1000-1700 nm) diagnostic
imaging and therapy.[99-101] Nonetheless, standalone organic
molecules often lack traits like tumor-targeting ability and water
solubility. Addressing these challenges involves employing strategies
such as PEGylation or generating nanometric forms. These approaches not
only prevent rapid renal or hepatic clearance of organic dyes but also
extend their circulation within the bloodstream. Furthermore, these NPs
tend to accumulate effectively in tumor tissues due to the enhanced
permeability and retention (EPR) effect.[102-104] Hu et al. employed
D–A molecular engineering to fabricate efficient small organic
molecules termed TD1 via anchoring the electron deficient
thiadiazolobenzotriazole (TBZ) core with 2,2′-bithiophene,
triphenylamine (TPhT) rotors, and encapsulated within lipid carriers,
creating mitochondria-targeted NPs known as M-TD1 NPs for MPTT.
Mechanistically, the improved mild thermal treatment at the
mitochondrial level triggers apoptosis-dependent cell death and
modulates cancer cell autophagy.[105] These combined effects lead to
an intensified eradication of cancer cells and a concurrent suppression
of cancer cell migration. Liu et al. introduced a novel concept of NIR
responsive and dual-sensitized NPs centered around a chromophore
combination of two perylene monoimides and a diamino anthraquinone
(2PMI-AQ), forming an inner hydrophobic core. To harness the sensitized
functionality, the hydrophilic thermosensitive polymers were
incorporated into the modified 2PMI-AQ, resulting in the formation of
stable NPs referred to as NP1. The external thermosensitive NP1
facilitate the loading and controlled photothermal release of HSP90
inhibitors.[106] Upon NIR laser irradiation, the synergistic effects
of photothermal and photodynamic actions are harnessed alongside the
controlled release of HSP90 inhibitors, thereby enhancing both MPTT and
photodynamic therapy (PDT) efficacy. Sun et al. reported an engineered
probes comprise two distinct
H2O2-activatable PTAs, namely aza-BOD-B1
with a single activatable site and aza-BOD-B2 with multiple activatable
sites. Upon interaction with H2O2,
aza-BOD-B1 demonstrates a modest absorption redshift of 60 nm, spanning
from 750 nm to 810 nm. However, this shift results in significant
spectral overlap, leading to only a mild photothermal effect on normal
tissues when subjected to 808 nm light irradiation. In contrast,
aza-BOD-B2 exhibits a substantial absorption spectral separation
spanning 150 nm, ranging from 660 nm to 810 nm.[107] This impressive
spectral separation facilitates genuine selective activation, thereby
minimizing the risk of side effects during cancer-focused MPTT. This
study represents a practical solution to the persisting challenge of
undesired side effects in MPTT, marking a significant stride forward in
the realm of precision medicine. Zhu et al. introduced a novel approach
to formulating a MPTT nanotherapeutic platform by utilizing the
self-assembly of a pH-responsive phenothiazinium dye with an impressive
PCE of up to 84.5%. Remarkably, they require an exceptionally low light
dose of only 36 J/cm² to achieve efficient MPTT of bacteria at pH 5.5,
achieved through 650 nm laser irradiation. Furthermore, this intelligent
nanoplatform exhibited a unique property of transitioning from a
negative to a positive charge in acidic biofilm environments. This
characteristic allowed for effective penetration and highly efficient
eradication of drug-resistant E. coli biofilms when subjected to
photoirradiation. The effectiveness of this nanoplatform was further
validated through in vivo animal tests, demonstrating its capacity for
bacterial elimination and mitigation of inflammation. Importantly, these
PTAs also showcased excellent biocompatibility and biosafety during the
treatment of ocular bacterial infections (Figure 2).[108] In
conclusion, this efficient single-component MPTT system, characterized
by its straightforward construction processes, holds immense potential
for widespread applications and eventual clinical translation.