Imaging-guided Photothermal Therapy Research Articles

Lipid-coated CaCO3-PDA nanoparticles as a versatile nanocarrier to enable pH-responsive dual modal imaging-guided combination cancer therapy.

Development of an intelligent and versatile delivery system to achieve tumor-targeted delivery and controlled release of diverse functional moieties is of great significance to realize precise cancer theranostics. In this study, we use pH-dissociable calcium carbonate-polydopamine (pCaCO3) nanocomposites as a template to guide the formation of a lipid bilayer on their surface, yielding lipid-coated pCaCO3 nanoparticles with high loading efficacies towards gadolinium ions (Gd3+), doxorubicin (DOX) and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR). The obtained liposomal nanotheranostics show excellent physiological stability and pH-dependent release of DOX and Gd3+; the latter could lead to pH-dependent T1 signal enhancement under magnetic resonance (MR) imaging, as well as efficient photothermal conversion efficacy. Then, we found that tumors in mice with intravenous injection of DiR-DOX-Gd@pCaCO3-PEG could be clearly visualized in a real-time manner by recording their near-infrared (NIR) fluorescence and T1 MR signal. Furthermore, treatment with such liposomal nanotheranostics injection and NIR laser irradiation could enable collective suppression of the growth of 4T1 tumors in Balb/c mice via combined chemo- and photothermal therapies. Therefore, this work highlights the concise preparation of lipid-coated pCaCO3 nanocomposites, which could be utilized for the construction of diverse cancer nanotheranostics by exploiting their versatile loading capacities.

Ultrasmall AgBiSe2 nanodots for CT/thermal imaging-guided photothermal tumor therapy in the NIR-II biowindow.

Stimulus-responsive ternary chalcogenide nanomaterials are regarded as promising 'all-in-one' nanotheranostics agents on account of their tunable band structures and multi-metal intrinsic properties. Herein, ultrasmall AgBiSe2 nanodots are prepared by a simple thermal injection method. It shows a narrow band gap of 0.91 eV and high absorption coefficient in the NIR-II biowindow, resulting in excellent photothermal performance. Under the irradiation of a 1064 nm laser, AgBiSe2 can induce the overexpression of intracellular heat shock protein (Hsp70) and cell apoptosis to inhibit the growth of tumor cells. The strong signal from CT/thermal imaging also provides guidance for tumor diagnosis. Importantly, AgBiSe2 can be rapidly excreted from the body, thus avoiding long term toxicity. This study presents the first biomedical application of AgBiSe2 nanodots in cancer treatment and extends the development of ternary chalcogenide-based semiconductor nanomedicine.

Enhanced delivery of theranostic liposomes through NO-mediated tumor microenvironment remodeling.

Highly efficient delivery of nanoagents to the tumor region remains the primary challenge for cancer nanomedicine. Herein, we propose a NO-mediated tumor microenvironment (TME) remodeling strategy for the high-efficient delivery of nanoagents into tumor. Quantum dots (QDs) with bright fluorescence in the near-infrared IIb (NIR-IIb, 1500-1700 nm) window and high photothermal conversion efficiency were encapsulated into liposomes for the imaging-guided photothermal therapy (PTT) of tumor. The fabrication of PEG and arginine-glycine-aspartate (RGD) peptide on liposomes ensured the prolonged circulation in vivo and active targeting to tumor. Moreover, the loading of a natural NO generator L-arginine in liposomes realized the continuous generation of NO in the acidic TME. By co-localization fluorescence imaging and western blot of tumor tissue, we confirmed that the release of NO activated the expression of metalloproteinases in TME and further degraded Collagen I in the peripheral region of the tumor, thus removing the barrier for the permeation of liposomes. Attributed to the enhanced accumulation of liposomes inside the tumor, NIR IIb imaging-guided PTT was achieved with remarkable therapeutic efficacy.

Stable twisted conformation aza-BODIPY NIR-II fluorescent nanoparticles with ultra-large Stokes shift for imaging-guided phototherapy.

Fluorescence imaging in the second near-infrared window (NIR-II, 1000-1700 nm) holds great promise for in vivo imaging and imaging-guided phototherapy with deep penetration and high spatiotemporal resolution. It is very appealing to obtain NIR-II fluorescent probes through simple procedures and economical substrates. Herein, we developed a D-A-D' structure NIR-II photosensitizer (triphenylamine modified aza-Bodipy, TAB) based on the strong electron-withdrawing nature of borane difluoride azadipyrromethene's center (aza-BODIPY). Subsequently, halogen atoms (Br, I) were introduced to the TAB molecule, and TAB-2Br and TAB-2I were synthesized. Compared to the TAB molecule, a significant redshift in the emission wavelength, ultra-large Stokes shift (>300 nm), and enhanced singlet oxygen production capacity were acquired for the halogenated molecules. After self-assembly of TABs and an amphiphilic polypeptide POEGMA23-PAsp20, the obtained P-TAB, P-TAB-2Br, and P-TAB-2I nanoparticles exhibited excellent water solubility and biocompatibility, remarkable photothermal conversion efficiency (beyond 40%), and good resistance to photobleaching, heat, and H2O2. Under 808 nm laser irradiation, the P-TAB-2I exhibited an efficient photothermal effect and ROS generation in vitro. And in vivo experiments revealed that P-TAB-2I displayed efficient NIR-II fluorescence imaging and remarkable tumor ablation results. All of these results make TAB-2I potential organic probes for clinical NIR-II fluorescence imaging and cancer phototherapy.

In situ formation of J-aggregate in the tumor microenvironment using acidity responsive polypeptide nanoparticle encapsulating galactose-conjugated BODIPY dye for NIR-II phototheranostics.

Through the activation of packing arrangements of dyes to modulate their photophysical and/or photochemical properties, not only new NIR-II dyes but tumor-specific NIR-II imaging and therapy can also be achieved. Herein, we designed an acid-responsive polypeptide nanoparticle (P-ipr@Gal) encapsulated with a pH-sensitive amphiphilic polypeptide (P-ipr) as a carrier for the galactose-conjugated BODIPY (Gal-BDP) dye. When P-ipr@Gal NPs are enriched in tumor regions by the EPR effect, the acidic microenvironment (pH 6.4-6.8) promotes the disintegration of P-ipr@Gal nanomicelles and the release of sufficient Gal-BDP. The protonation of the julolidine nitrogen of the Gal-BDP dye switched on the molecular stacking transformation from the H-aggregate to J-aggregate. The J-aggregate significantly enhanced the redshift absorption and emission intensity, which enhanced the fluorescence brightness and photothermal therapeutic effect in the tumor region. We also prepared J-aggregates PAsp@Gal with non-acidic responsive polyaspartic acid benzyl esters (PAsp) encapsulated Gal-BDP, which remained "always-on" with J-aggregate characteristics. The P-ipr@Gal (or PAsp@Gal) J-aggregate has a maximum emission peak redshifted to nearly 1064 nm, with a 3.5-fold increase in the emission intensity compared to the H-aggregate at pH 7.4. Based on the effective accumulation of tumor sites and considerable PCE (>40%), P-ipr@Gal nanoparticles have a lower background and higher tumor background ratio, which makes them a potential NIR-II imaging-guided photothermal therapy agents.

A hypoxia-responsive supramolecular formulation for imaging-guided photothermal therapy.

Photothermal agents (PTAs) based on organic small-molecule dyes emerge as promising theranostic strategy in imaging and photothermal therapy (PTT). However, hydrophobicity, photodegradation, and low signal-to-noise ratio impede their transformation from bench to bedside. In this study, a novel supramolecular PTT formulation by a stimuli-responsive macrocyclic host is prepared to overcome these obstacles of organic small-molecule PTAs.Methods: Sulfonated azocalix[4]arene (SAC4A) was synthesized as a hypoxia-responsive macrocyclic host. Taking IR780 as an example, the supramolecular nanoformulation IR780@SAC4A was constructed by grinding method, and its solubility, photostability, and photothermal conversion were evaluated. The hypoxia tumor-selective imaging and supramolecular PTT of IR780@SAC4A were further evaluated in vitro and in vivo.Results: IR780@SAC4A is capable of enhancing the solubility, photostability, and photothermal conversion of IR780 significantly, which achieve this supramolecular formulation with good imaging-guided PTT efficacy in vitro and in vivo.Conclusions: This study demonstrates that the supramolecular PTT strategy is a promising cancer theranostic method. Moreover, this supramolecular approach is applicative to construct kinds of supramolecular PTAs, opening a general avenue for extending smart PTT formulations.

Supramolecular J-aggregates of aza-BODIPY by steric and π-π nteractions for NIR-II phototheranostics.

Achieving J-aggregation of a molecule is a fascinating way to construct fluorescent imaging and photothermal therapy agents in the second near-infrared window. Modulation of the balance between intermolecular π-π stacking and steric interactions is an elegant method to acquire J-aggregation dyes. Herein, we succeeded in synthesizing an aza-BODIPY dye with J-aggregation characteristics by introducing steric hindrance (TPA) and a π-bridge (thiophene) in the aza-BODIPY skeleton. In aqueous solutions, supramolecular J-aggregates with a regular lamellar stacking structure could quickly be formed by the dye-templated self-assembly and longer absorption (λmax = 939 nm) and emission (λmax = 1039 nm) bands were observed. After co-assembly of the dye and an amphiphilic polypeptide (POEGMA23-PAsp20), the obtained J-aggregation nanoparticles (J-NPs) with good water solubility and smaller size were more suitable for application in living organisms. In addition, the J-NPs exhibited good stability, considerable photothermal conversion capacity (η = 35.6%), and excellent resistance to pH, H2O2, and photobleaching. In vitro and in vivo experiments revealed that the J-NPs show great NIR-II fluorescence imaging capabilities and anti-tumor effects under 915 nm irradiation (1 W cm-2). This is a rare example of using BODIPY dyes to perform NIR-II fluorescence imaging-guided photothermal therapy under NIR-II irradiation.

Galactose conjugated boron dipyrromethene and hydrogen bonding promoted J-aggregates for efficiently targeted NIR-II fluorescence assistant photothermal therapy

It is essential to develop novel multifunctional and easily synthesized stable NIR-II fluorescent probes to guide photothermal therapy for tumors. Here, we propose a new strategy to construct boron dipyrromethene (BODIPY) J-aggregates by intermolecular hydrogen bonding (H-bond) and π-π stacking interactions to achieve fluorescence emission in the second near-infrared window (NIR-II, 1000–1700 nm). A novel meso-benzamide galactose hexanoate-BODIPY (Gal-OH-BDP) amphiphilic small molecular dye was synthesized and it formed nanoparticles spontaneously in aqueous solution with a maximum emission wavelength near 1060 nm, which works as a smart nanomedicine for targeting NIR-II imaging-guided photothermal therapy (PTT) of hepatocellular carcinoma. Galactose not only provided hydrogen bonds to regulate the aggregation pattern of the molecules but also effectively targeted hepatocellular carcinoma cells and promoted the formation of well-dispersed nanoparticles of dye molecules due to their hydrophilicity. Moreover, due to high photothermal conversion efficiency (PCE = 55%), Gal-OH-BDP NPs achieve galactose-targeted NIR-II imaging and PTT, which is important for the precise diagnosis and treatment of tumors (Scheme 1). In the present research work, H-bond was introduced for the first time into BODIPY for building J-aggregates to achieve the NIR-II fluorescence.

NIR/MRI-Guided Oxygen-Independent Carrier-Free Anti-Tumor Nano-Theranostics.

Imaging-guided photothermal therapy (PTT)/photodynamic therapy (PDT) for cancer treatment are beneficial for precise localization of the malignant lesions and combination of multiple cell killing mechanisms in eradicating stubborn thermal-resistant cancer cells. However, overcoming the adverse impact of tumor hypoxia on PDT efficacy remains a challenge. Here, carrier-free nano-theranostic agents are developed (AIBME@IR780-APM NPs) for magnetic resonance imaging (MRI)-guided synergistic PTT/thermodynamic therapy (TDT). Two IR780 derivatives are synthesized as the subject of nanomedicine to confer the advantages for the nanomedicine, which are by feat of amphiphilic IR780-PEG to enhance the sterical stability and reduce the risk from reticuloendothelial system uptake, and IR780-ATU to chelate Mn2+ for T1 -weighted MRI. Dimethyl 2,2'-azobis(2-methylpropionate) (AIBME), acting as thermally decomposable radical initiators, are further introduced into nanosystems with the purpose of generating highly cytotoxic alkyl radicals upon PTT launched by IR780 under 808nm laser irradiation. Therefore, the sequentially generated heat and alkyl radicals synergistically induce cell death via synergistic PTT/TDT, ignoring tumor hypoxia. Moreover, these carrier-free nano-theranostic agents present satisfactory biocompatibility, which could be employed as a powerful weapon to hit hypoxic tumors via MRI-guided oxygen-independent PTT and photonic TDT.

Ultrasmall PEI-Decorated Bi2Se3 Nanodots as a Multifunctional Theranostic Nanoplatform for in vivo CT Imaging-Guided Cancer Photothermal Therapy.

Bi-based nanomaterials, such as Bi2Se3, play an important part in biomedicine, such as photothermal therapy (PTT) and computed tomography (CT) imaging. Polyethylenimine (PEI)-modified ultrasmall Bi2Se3 nanodots were prepared using an ultrafast synthetic method at room temperature (25°C). Bi2Se3 nanodots exhibited superior CT imaging performance, and could be used as effective photothermal reagents owing to their broad absorption in the ultraviolet–visible–near infrared region. Under irradiation at 808 nm, PEI-Bi2Se3 nanodots exhibited excellent photothermal-conversion efficiency of up to 41.3%. Good biocompatibility and significant tumor-ablation capabilities were demonstrated in vitro and in vivo. These results revealed that PEI-Bi2Se3 nanodots are safe and a good nanotheranostic platform for CT imaging-guided PTT of cancer.

Preparation of composite nanoprobe PB/CS by in-situ catalytic polymerization and study on its photothermal performance

Photothermal therapy (PTT) is a new treatment, and photoacoustic (PA) imaging-guided PTT has aroused extensive attention recently. Poly-2-phenyl-benzobisthiazole (PB) is a new type of conjugated polymer with good biocompatibility and excellent photothermal properties similar to single-walled CNT. However, the poor hydrophilicity of PB limits its application in biomaterials. In this work, chitosan-Cu(II) network structure was first constructed, and then the Cu(II) in-situ initiated the polymerization of aminobenzenedithiophenol and terephthalonitrile to obtain chitosan/PB composite. The excellent hydrophilicity of chitosan-based nanoparticle has successfully improved the water solubility of the obtained nanoprobe PB/CS. Additionally, PB/CS has an excellent PA signal. Thus, a simple and convenient nanosystem was fabricated and applied for PA imaging-guided PTT.

Cancer cell membrane-coated nanoparticles for bimodal imaging-guided photothermal therapy and docetaxel-enhanced immunotherapy against cancer

BackgroundMono-therapeutic modality has limitations in combating metastatic lesions with complications. Although emerging immunotherapy exhibits preliminary success, solid tumors are usually immunosuppressive, leading to ineffective antitumor immune responses and immunotherapeutic resistance. The rational combination of several therapeutic modalities may potentially become a new therapeutic strategy to effectively combat cancer.ResultsPoly lactic-co-glycolic acid (PLGA, 50 mg) nanospheres were constructed with photothermal transduction agents (PTAs)-Prussian blue (PB, 2.98 mg) encapsulated in the core and chemotherapeutic docetaxel (DTX, 4.18 mg)/ immune adjuvant-imiquimod (R837, 1.57 mg) loaded in the shell. Tumor cell membranes were further coated outside PLGA nanospheres (designated “M@P-PDR”), which acted as “Nano-targeted cells” to actively accumulate in tumor sites, and were guided/monitored by photoacoustic (PA)/ magnetic resonance (MR) imaging. Upon laser irradiation, photothermal effects were triggered. Combined with DTX, PTT induced in situ tumor eradication. Assisted by the immune adjuvant R837, the maturation rate of DCs increased by 4.34-fold compared with that of the control. In addition, DTX polarized M2-phenotype tumor-associated macrophages (TAMs) to M1-phenotype, relieving the immunosuppressive TME. The proportion of M2-TAMs decreased from 68.57% to 32.80%, and the proportion of M1-TAMs increased from 37.02% to 70.81%. Integrating the above processes, the infiltration of cytotoxic T lymphocytes (CTLs) increased from 17.33% (control) to 35.5%. Primary tumors and metastasis were significantly inhibited when treated with “Nano-targeted cells”-based cocktail therapy.Conclusion“Nano-targeted cells”-based therapeutic cocktail therapy is a promising approach to promote tumor regression and counter metastasis/recurrence.Graphical

Boron difluoride formazanate dye for high‐efficiency NIR‐II fluorescence imaging‐guided cancer photothermal therapy

The small molecular second near-infrared (NIR-II, 1000–1700 nm) dye-based nanotheranostics can concurrently combine deep-tissue photodiagnosis with in situ phototherapy, which occupies a vital position in the early detection and precise treatment of tumors. However, the development of small molecular NIR-II dyes is still challenging due to the limited electron acceptors and cumbersome synthetic routes. Herein, we report a novel molecular electron acceptor, boron difluoride formazanate (BDF). Based on BDF, a new small molecular NIR-II dye BDF1005 is designed and synthesized with strong NIR-I absorption at 768 nm and bright NIR-II peak emission at 1034 nm. In vitro and in vivo experiments demonstrate that BDF1005-based nanotheranostics can be applied for NIR-II fluorescence imaging-guided photothermal therapy of 4T1 tumor-bearing mice. Under 808 nm laser irradiation, tumor growth can be effectively inhibited. This work opens up a new road for the exploitation of NIR-II small molecular dyes for cancer phototheranostics.

Biologically excretable AIE nanoparticles wear tumor cell-derived “exosome caps” for efficient NIR-II fluorescence imaging-guided photothermal therapy

Nanoparticles (NPs) assisted photothermal therapy (PTT) is a promising cancer treatment modality and has attracted the attention of the scientific mainstream. However, developing bio-excretable NPs that exhibit efficient optical properties and specific tumor targeting capability simultaneously is difficult. Herein, we develop a kind of hybrid nanovesicles consisting of bio-excretable aggregation-induced emission (AIE) NPs and tumor cell-derived “exosome caps” (TT3-oCB NP@EXOs) with enhanced second near-infrared (NIR-II, 900–1700 nm) fluorescence property and PTT functionality via electroporation. Compared with TT3-oCB NPs, TT3-oCB NP@EXOs exhibit excellent biocompatibility, specific targeting ability in vitro, homing to homologous tumors in vivo, and prolonged circulation time. Furthermore, TT3-oCB NP@EXOs were utilized as biomimetic NPs for NIR-II fluorescence imaging-guided PTT of tumors, due to their high and stable photothermal conversion capacity under 808 nm irradiation. Therefore, with the validation of other AIE NPs with poor targeting property, the tumor cell-derived EXO/AIE NP hybrid nanovesicles may provide an alternative artificial targeting strategy for improving tumor diagnosis and PTT.

Thiadiazoloquinoxaline-Based Semiconducting Polymer Nanoparticles for NIR-II Fluorescence Imaging-Guided Photothermal Therapy.

Phototheranostics have gained more and more attention in the field of cancer diagnosis and therapy. Among a variety of fluorophores for phototheranostics, semiconducting polymer nanoparticles (SPNs), which are usually constructed by encapsulating hydrophobic semiconducting polymers (SPs) with amphiphilic copolymers, have shown great promise. As second near-infrared (NIR-II) fluorescence imaging has both higher imaging resolution and deeper tissue penetration compared with first near-infrared (NIR-I) fluorescence imaging, NIR-II fluorescent SPNs have been widely designed and prepared. Among numerous structural units for semiconducting polymers (SPs) synthesis, thiadiazoloquinoxaline (TQ) has been proved as an efficient electron acceptor unit for constructing NIR-II fluorescent SPs by reacting with proper electron donor units. Herein, we summarize recent advances in TQ-based SPNs for NIR-II fluorescence imaging-guided cancer photothermal therapy. The preparation of TQ-based SPNs is first described. NIR-II fluorescence imaging-based and multimodal imaging-based phototheranostics are sequentially discussed. At last, the conclusion and future perspectives of this field are presented.

A novel ICG-labeled cyclic TMTP1 peptide dimer for sensitive tumor imaging and enhanced photothermal therapy in vivo

TMTP1 is a polypeptide independently screened in our laboratory, which can target tumors in situ and metastases. In previous work, we have successfully developed a near-infrared (NIR) probe TMTP1-PEG4-ICG for tumor imaging. However, the limited ability to target tumor micrometastases hinders its further clinical application. Multimerization of peptides has been extensively demonstrated as an effective strategy to increase receptor binding affinity due to “multivalent effect” or “apparent cooperative affinity”. In this study, a novel TMTP1 homodimer-directed NIR probe (TMTP1-PEG4)2-ICG was successfully constructed and synthesized. The cyclic TMTP1 peptides were bridged by two PEG4 linkers and then labeled with ICG-NHS for tumor imaging and photothermal therapy. In vivo biodistribution were assessed in normal BALB/c mice, and tumor targeting abilities of (TMTP1-PEG4)2-ICG and its monomer were evaluated and compared in 4T1-bearing subcutaneous tumor and lymph node metastasis model mice. Biodistribution analysis in vivo revealed that (TMTP1-PEG4)2-ICG was cleared mainly in both liver and kidney dependent way. Comparing with free ICG dye or TMTP1-PEG4-ICG probe, this improved (TMTP1-PEG4)2-ICG dimer showed more sensitive tumor imaging and could clearly identify tumors at a minimum volume of 10 mm3. Additionally, when compared to its monomer, lymph node (LN) metastases could also be apparently visualized and easily distinguished from normal LN by the novel dimer at 24 h post-injection. The blocking study revealed that the tumor accumulation of this probe was specifically medicated by receptor-ligand interaction. Furthermore, with the increase in stability and tumor targeting ability of ICG in vivo, the probe could also be an attractive photothermal agent to significantly inhibit tumor growth under 808 nm NIR laser irradiation. In conclusion, our work revealed that the novel (TMTP1-PEG4)2-ICG dimer could be a promising theranostic agent for sensitive tumor imaging and imaging-guided photothermal therapy, indicating its broad prospects for further clinical transformation.

Development of Nickel Selenide@polydopamine Nanocomposites for Magnetic Resonance Imaging Guided NIR-II Photothermal Therapy.

The penetration depth of near-infrared laser has greatly restricted the development of most photothermal agents. Recently, photothermal agents in the second near-infrared (NIR-II) window have drawn great attention as they can overcome above barrier. Herein, a novel "all in one" NIR-II responsive nanoplatform (nickel selenide @polydopamine nanocomposites, NiSe@PDA NCs) based on in situ coating the polydopamine (PDA) on the surface of biomineralized nickel selenide nanoparticles (NiSe NPs) for dual-model imaging-guided photothermal therapy is reported. Under the illumination of NIR-II laser (1064nm), the photothermal conversion efficiency of NiSe@PDA NCs can reach 48.4%, which is higher than that of single NiSe NPs due to the enhanced molar extinction coefficient. In addition, because of the paramagnetic effect of NiSe NPs, the constructed NiSe@PDA NCs can be acted as T1 contrast agent for magnetic resonance imaging (MRI). Most importantly, the MRI contrast effect is enhanced with the coating of PDA layer due to the loose structure of PDA. Ultimately, both in vitro and in vivo experiments demonstrate that the developed NCs can achieve efficient MRI-guided photothermal therapy for treating malignant tumor. Therefore, the designed NiSe@PDA NCs with excellent features show great potential for clinical MRI-guided cancer therapy.

"Internal and External Combined" Nonradiative Decay-Based Nanoagents for Photoacoustic Image-Guided Highly Efficient Photothermal Therapy.

Rational manipulation of nonradiative decay channels is of crucial significance to improve photothermal conversion efficiency (PCE) and design photothermal agents. We first used the "internal and external combined" nonradiative decay strategy to enhance PCE. Specifically, organic IR-Y6 NPs with strong NIR absorption and high molar extinction coefficient were prepared and characterized. By means of TD-DFT calculations and fs-TA spectroscopy, the dual nonradiative decay channels composed of the free rotor (external strategy) and ultrafast dark excited states (DESs) between S0 and S1 states (internal strategy) were proved, which significantly enhanced PCE, up to 66%. IR-Y6 NPs were applied to a mice tumor model for photoacoustic image-guided photothermal therapy, showing complete tumor ablation ability and good biocompatibility for the normal organs. This work is of significance to deeply understand the nonradiation decay mechanism and rational design of high-performance PTT agents.

Side chain engineering of semiconducting polymers for improved NIR-II fluorescence imaging and photothermal therapy

Development of efficient agents for NIR-II fluorescence imaging (NIR-II FI) offers opportunities to facilitate NIR-II FI in biomedicine and life science. Although semiconducting polymers (SPs) are proved to be excellent candidates for NIR-II FI, their fluorescence quantum yields are generally low mainly because of the accelerated nonradiative decay by the vibrational overlap between the ground state and excited state due to the small energy gap of NIR-II SPs. We herein propose a side chain engineering of SPs for enhanced NIR-II FI and imaging-guided photothermal therapy (PTT). The fluorescence optimization is realized by tuning the conformation and bulk of side chains of SPs, which demonstrates that the bulky branched side chains remarkably contribute to the fluorescence enhancement relative to linear or short branched side chains. Density functional theory (DFT) calculation indicates that bulky branched side chain-attached SP (P3) has the largest dihedral angle between electron donor and acceptor units, which suggests the largest intramolecular steric hindrance that restricts the free rotation in the molecule, thus boosting the radiative decay to generate fluorescence. Water-dispersible nanoparticles with high tumor specificity fabricated from the optimal P3 are employed for in vivo applications, which show excellent NIR-II FI performance and PTT efficacy toward tumor. Our study therefore proposes a feasible molecular guideline to amplify the NIR-II brightness of SPs for improved phototheranostics.

Promoted intramolecular photoinduced-electron transfer for multi-mode imaging-guided cancer photothermal therapy

Promoted intramolecular photoinduced-electron transfer for multi-mode imaging-guided cancer photothermal therapy