Size Modulation of Conjugated Polymer Nanoparticles for Improved NIR-II Fluorescence Imaging and Photothermal Therapy.

Near-infrared-II fluorescence imaging (NIR-II FI) has become a powerful imaging technique for disease diagnosis owing to its superiorities, including high sensitivity, high spatial resolution, deep imaging depth, and low background interference. Despite the widespread application of conjugated polymer nanoparticles (CPNs) for NIR-II FI, most of the developed CPNs have quite low NIR-II fluorescence quantum yields based on the energy gap law, which makes high-sensitivity and high-resolution imaging toward deep lesions still a huge challenge. This work proposes a nanoengineering strategy to modulate the size of CPNs aimed at optimizing their NIR-II fluorescence performance for improved NIR-II phototheranostics. By adjusting the initial concentration of the synthesized conjugated polymer, a series of CPNs with different particle sizes are successfully prepared via a nanoprecipitation approach. Results show that the NIR-II fluorescence brightness of CPNs gradually amplifies with decreasing particle size, and the optimal CPNs, NP0.2, demonstrate up to a 2.05-fold fluorescence enhancement compared with the counterpart nanoparticles. With the merits of reliable biocompatibility, high photostability, and efficient light-heat conversion, the optimal NP0.2 has been successfully employed for NIR-II FI-guided photothermal therapy both in vitro and in vivo. Our work highlights an effective strategy of nanoengineering to improve the NIR-II performance of CPNs, advancing the development of NIR-II FI in life sciences.

A Mitochondria-Targeted NIR-II Molecule Fluorophore for Precise Cancer Phototheranostics.

Subcellular organelle mitochondria are becoming a key player and a driver of cancer. Mitochondrial targeting phototheranostics has attracted increasing attention for precise cancer therapy. However, those phototheranostic systems still face great challenges, including complex and multiple components, light scattering, and insufficient therapeutic efficacy. Herein, a molecular fluorophore IR-TPP-1100 was tactfully designed by molecular engineering for mitochondria-targeted fluorescence imaging-guided phototherapy in the second near-infrared window (NIR-II). IR-TPP-1100 not only exhibited prominent photophysical properties and high photothermal conversion efficiency but also achieved excellent mitochondria-targeting ability. The mitochondria-targeting IR-TPP-1100 enabled NIR-II fluorescence and photoacoustic dual-modality imaging of mitochondria at the organism level. Moreover, it integrated photothermal and photodynamic therapy, obtaining remarkable tumor therapeutic efficacy by inducing mitochondrial apoptosis. These results indicate that IR-TPP-1100 has great potential for precise cancer therapy and provides a promising strategy for developing mitochondria-targeting NIR-II phototheranostic agents.

Phenylboronic Acid-Modified Near-Infrared Region II Excitation Donor-Acceptor-Donor Molecule for 2-Deoxy-d-Glucose Improved Starvation/Chemo/Photothermal Combination Therapy.

Synergistic chemotherapy and photothermal therapy (PTT) have emerged as a promising anticancer paradigm to achieve expected therapeutic effects while mitigating side effects. However, the chemo/PTT combination therapy suffers from limited penetration depth, thermoresistance performance of tumor cells, and low drug bioavailability. Herein, multifunctional nanoparticles (BTP/DOX/2DG NPs) coloaded with near-infrared region II (NIR-II) light excitation donor-acceptor-donor (D-A-D) small molecules, doxorubicin (DOX), and 2-deoxy-d-glucose (2-DG) are developed for reinforced starvation/chemo/NIR-II PTT combination therapy. The synthesized phenylboronic acid (PBA)-modified water-soluble D-A-D molecule (BBT-TF-PBA) not only exhibits high binding ability to DOX and 2-DG through donor-acceptor coordination interactions PBA-diol bonds but also serves as a photoactive agent for NIR-II fluorescence imaging, NIR-II photoacoustic imaging, and NIR-II PTT. Under the acidic and oxidizing conditions in the tumor microenvironment, donor-acceptor coordination interactions and PBA-diol bond are decomposed, simultaneously releasing DOX and 2-DG from BTP/DOX/2DG NPs to achieve effective chemotherapy and starvation therapy. 2-DG also effectively inhibits the expression of heat shock protein and further enhances NIR-II PTT and chemotherapy efficiency. In vitro and in vivo experiments demonstrate the combination effect of BTP/DOX/2DG NPs for chemotherapy, NIR-II PTT, and starvation therapy.

Photoactive oligomer with D-D'-A-D'-D''-D'-A-D'-D scaffold for high-efficiency NIR-II phototheranostics.

A D-D'-A-D'-D''-D'-A-D'-D type photoactive oligomer (O-BT) based nanoparticles (NPs) were prepared for biomedical application. The O-BT NPs possessed a high extinction coefficient, excellent hyperthermia generation ability, satisfactory NIR-II fluorescence emission, and good batch-to-batch reproducibility, and could be used as high-efficiency phototheranostics for photothermal therapy and NIR-II fluorescence imaging.

Early diagnosis and treatment of osteoarthritis with a Au@PDA-WL NP nano-probe by photoacoustic imaging.

A photoacoustic imaging (Au@PDA-WL NPs) probe was successfully prepared for monitoring the early degeneration of articular cartilage. WYRGRL immobilized on the surface of Au@PDA NPs could target the collagen II peptide, which is expressed on chondrocytes in vivo and in vitro, and the enrichment of this nano-probe on cartilage tissue further resulted in the localized plasmon resonance coupling effect, inducing an enhancement in photothermal conversion capacity after the formation of aggregates. Besides, the catechol structure in the PDA shell could eliminate ROS to effectively delay the development of osteoarthrosis.

Self-delivery of metal-coordinated NIR-II nanoadjuvants for multimodal imaging-guided photothermal-chemodynamic amplified immunotherapy.

The effectiveness of phototheranostics induced immunotherapy is still hampered by limited light penetration depth, the complex immunosuppressive tumor microenvironment (TME) and the low efficiency of immunomodulator drug delivery. Herein, self-delivery and TME responsive NIR-II phototheranostic nanoadjuvants (NAs) were fabricated to suppress the growth and metastasis of melanoma through the integration of photothermal-chemodynamic therapy (PTT-CDT) and immune remodeling. The NAs were constructed by the self-assembly of ultrasmall NIR-II semiconducting polymer dots and the toll-like receptor agonist resiquimod (R848) utilizing manganese ions (Mn2+) as coordination nodes. Under acidic TME, the NAs responsively disintegrated and released therapeutic components, which enable NIR-II fluorescence/photoacoustic/magnetic resonance imaging-guided tumor PTT-CDT. Moreover, the synergistic treatment of PTT-CDT could induce significant tumor immunogenic cell death and evoke highly efficacious cancer immunosurveillance. The released R848 stimulated the maturation of dendritic cells, which both amplified the antitumor immune response by modulating and remodeling the TME. The NAs present a promising integration strategy of polymer dot-metal ion coordination and immune adjuvants for precise diagnosis and amplified anti-tumor immunotherapy against deep-seated tumors. STATEMENT OF SIGNIFICANCE: The efficiency of phototheranostics induced immunotherapy is still limited by insufficient light penetration depth, low immune response and the complex immunosuppressive tumor microenvironment (TME). In order to improve the efficacy of immunotherapy, self-delivery NIR-II phototheranostic nanoadjuvants (PMR NAs) were successfully fabricated via the facile coordination self-assembly of ultra-small NIR-II semiconducting polymer dots and toll-like receptor agonist resiquimod (R848) utilizing manganese ions (Mn2+) as coordination nodes. PMR NAs not only enable TME responsive cargo release and NIR-II fluorescence/photoacoustic/magnetic resonance imaging mediated precise localization of tumors, but also achieve synergistic photothermal-chemodynamic therapy, evoking an effective anti-tumor immune response by ICD effect. The responsively released R848 could further amplify the efficiency of immunotherapy by reversing and remodeling the immunosuppressive tumor microenvironment, thereby effectively inhibiting tumor growth and lung metastasis.

Molecular Oligomerization and Donor Engineering Strategies for Achieving Superior NIR-II Fluorescence Imaging and Thermotherapy under 1064 nm Laser Irradiation.

An enormous challenge still exists for designing molecules with the second near-infrared (NIR-II, 1000-1700 nm) window absorption, NIR-II fluorescence emission, and batch-to-batch reproducibility, which is the premise for high-performance NIR-II phototheranostics. Although organic small molecules and polymers have been largely explored for phototheranostics, it is difficult to satisfy the above three elements simultaneously. In this work, molecular oligomerization (the general structure is S-D-A-D'-A-D-S) and donor engineering (changing the donor linker D') strategies are applied to design phototheranostic agents. Such strategies are proved to be efficient in adjusting molecular configuration and energy level, affecting the optical and thermal properties. Three oligomers (O-T, O-DT, and O-Q) are further prepared into water-soluble nanoparticles (NPs). Particularly, the O-T NPs exhibit a higher molar extinction coefficient at 1064 nm (≈4.3-fold of O-DT NPs and ≈4.8-fold of O-Q NPs). Furthermore, the O-T NPs show the highest NIR-II fluorescence brightness and heating capacity (PCE = 73%) among the three NPs under 1064 nm laser irradiation and served as agents for NIR-II imaging guided in vivo photothermal therapy. Overall, by using molecular oligomerization and donor engineering strategies, a powerful example of constructing high-performance NIR-II phototheranostics for clinical translation is given.

NIR-II Excitation Phototheranostic Platform for Synergistic Photothermal Therapy/Chemotherapy/Chemodynamic Therapy of Breast Cancer Bone Metastases.

To improve bone metastases treatment efficacy, current strategies are focused on the integration of chemotherapy with phototheranostic. However, the success of phototheranostic approaches is hampered by the limited tissue penetration depth of near-infrared-I (NIR-I) light (700-900 nm). In this study, a NIR-II (1000-1700 nm) excitation phototheranostic (BTZ/Fe2+ @BTF/ALD) is presented for NIR-II fluorescence imaging and NIR-II photoacoustic imaging-guided NIR-II photothermal therapy (PTT), chemotherapy, and chemodynamic therapy (CDT) of breast cancer bone metastases. This phototheranostic is developed by integrating a dopamine-modified NIR-II absorbing donor-acceptor-donor small molecule (BBT-FT-DA), the boronate anticancer drug bortezomib (BTZ), and Fe2+ ions, as CDT catalysts, into an amphiphilic PEGylated phospholipid modified with the bone-targeting ligand alendronate. In acidic and hydrogen peroxide (H2 O2 ) over expression tumor microenvironment, the boronate-catechol linkage is cleaved and BTZ and Fe2+ ions are released to initiate the Fenton reaction, that is, chemotherapy and CDT, respectively, are initialized. It is confirmed using the murine 4T1 bone metastasis model that BTZ/Fe2+ @BTF/ALD significantly suppresses the progression of tumor cells in the bone tissue via a synergistic NIR-II PTT/chemotherapy/CDT effect. Overall, this work provides fresh insights to guide the development of NIR-II phototheranostics for breast cancer bone metastases.

Recent advances in small molecule dye-based nanotheranostics for NIR-II photoacoustic imaging-guided cancer therapy.

Photoacoustic (PA) imaging in the second near-infrared (NIR-II) window has gained more and more attention in recent years and showed great potential in the field of bioimaging. Until now, numerous materials have been developed as contrast agents for NIR-II PA imaging. Among them, small molecule dyes hold unique advantages such as definite structures and capability of fast clearance from body. By virtue of these advantages, small molecule dyes-constructed nanoparticles have relatively small size and show promise in the clinical translation. Thus, in this minireview, we summarize recent advances in small molecule dyes-based nanotheranostics for NIR-II PA imaging and cancer therapy. Studies about NIR-II PA imaging-guided phototherapy are first introduced. Then, NIR-II PA imaging-guided phototherapy-based combination therapeutic systems are reviewed. Finally, the conclusion and perspectives of this field are summarized and discussed.

Fabrication of a phototheranostic nanoplatform for single laser-triggered NIR-II fluorescence imaging-guided photothermal/chemo/antiangiogenic combination therapy.

Phototheranostics that integrates real-time optical imaging and light-controlled therapy has recently emerged as a promising paradigm for cancer theranostics. Herein, a new small molecule dye DPP-BT-TPA with strong emission above 1000 nm and a redox-responsive prodrug camptothecin-combretastatin A4 (CPT-CA4) were designed and successfully synthesized. A multifunctional phototheranostic nanoplatform was then fabricated by encapsulating them within an amphiphilic polymer. The presence of DPP-BT-TPA enabled high-resolution imaging in the second near-infrared window (NIR-II) and efficient photothermal therapy. The prodrug was cleaved by the overexpressed glutathione (GSH) in the tumor microenvironment to release the chemotherapeutic drug CPT and the angiogenesis inhibitor CA4. Because this process can be accelerated with elevated temperature, laser-induced hyperthermia was utilized to control the drug release and enhance the therapeutic effect. Tumors in living mice were observed through NIR-II imaging after intravenous injection of the obtained nanoparticles. Improved antitumor efficacy by photothermal/chemo/antiangiogenic combination therapy was achieved with a NIR laser both in vitro and in vivo. This work provides a promising strategy for developing tumor microenvironment responsive and light-controlled theranostic platforms. STATEMENT OF SIGNIFICANCE: Fluorescence imaging in the second near-infrared (NIR-II, 1000-1700 nm) window and near-infrared light-controlled drug release have been recognized as efficient strategies for cancer theranostics. Herein, we present a phototheranostic platform fabricated with a biocompatible NIR-II emissive dye DPP-BT-TPA and a redox-responsive prodrug camptothecin-combretastatin A4 (CPT-CA4). DPP-BT-TPA not only provides high-resolution NIR-II imaging in vivo but also enables efficient photothermal therapy. In addition, the photothermal effect largely accelerates the release of the chemotherapeutic drug CPT and the angiogenesis inhibitor CA4 in the glutathione-overexpressed tumor microenvironment. Thus, the designed phototheranostic platform can be used for NIR-II imaging-guided photothermal/chemo/antiangiogenic combination therapy for tumors with a single laser.

An AIPH-decorated semiconducting nanoagonist for NIR-II light-triggered photothermic/thermodynamic combinational therapy.

A multifunctional semiconducting nanoagonist with high photothermic conversion efficiency (86.2%) and alkyl radical generation ability was developed. The nanoagonist demonstrated excellent anticancer performance through NIR-II light-triggered photothermic/thermodynamic combinational therapy both in vitro and in vivo.

Novel Glutathione Activated Smart Probe for Photoacoustic Imaging, Photothermal Therapy, and Safe Postsurgery Treatment.

Preventing tumor recurrence is the most important target for cancer treatment. However, the current effective and advanced technology relies on the use of near-infrared region (NIR), and the equipment of NIR-I and NIR-II fluorescence imaging technique-based fluorescent-guided surgery is expensive and complicated to operate. Here, we report a safe and effective strategy of an organic-inorganic hybrid gold nanoparticle-based novel smart probe (Au@PDA-ss-PEGm NPs) which is appropriate for photoacoustic imaging (PAI) and plasmonic photothermal therapy (PPTT) of tumors in vivo. After intravenous injection, the probe would be transported to the tumor to penetrate the cellular membrane. Then the disulfide bond on the probe surface would be broken with the help of a high concentration of glutathione in the tumor cell. The remaining Au@PDA NPs would aggregate to form plasmonic nanoclusters and exhibit a notable plasmon coupling enhanced photothermal (PCEPT) effect. Besides, the results further proved its good biosafety and pharmacokinetic characteristics in vivo and, more important, a short time exposure under 808 nm laser after surgical removal of the tumor, which would be effective to prevent tumor recurrence and bring dawn to the high-efficiency treatment of tumors.

Capsaicin-Decorated Semiconducting Polymer Nanoparticles for Light-Controlled Calcium-Overload/Photodynamic Combination Therapy.

Calcium-overload cancer therapy has gained more and more attention owing to its good therapeutic efficacy with low side effect. However, conventional calcium-overload therapy is achieved by introducing an additional calcium element into the tumor site by nanomedicines, which may also lead to the calcium-overload of normal organs, causing an undesirable side effect. To address such issues, capsaicin-decorated semiconducting polymer nanoparticles (CSPN) are designed to modulate the calcium ion channel of cancer cells for calcium-overload cancer therapy without adding an additional calcium element. CSPN is composed of a near-infrared (NIR) absorbing semiconducting polymer (SP) PCPDTBT and a capsaicin-conjugated amphiphilic copolymer, PEG-PHEMA-Cap. Under NIR laser irradiation, PCPDTBT can generate singlet oxygen (1 O2 ), which not only triggers the release of capsaicin, but also induces photodynamic therapy (PDT). The released capsaicin can further activate transient receptor potential cation channel subfamily V member 1 (TRPV1) of U373 cancer cells, leading to an influx of calcium ions into cells. In addition, the intense NIR-II fluorescence signal of CSPN makes it suitable for tumor imaging. Thus, this study develops a tumor specific nanotheranostic system for NIR-II fluorescence imaging-guided calcium-overload/PDT combination therapy.

Semiconducting Polymer Nanoparticles for Photoactivatable Cancer Immunotherapy and Imaging of Immunoactivation.

Immunotherapy that stimulates the body's own immune system to kill cancer cells has emerged as a promising cancer therapeutic method. However, some types of cancer exhibited a low response rate to immunotherapy, and the high risk of immune-related side effects has been aroused during immunotherapy, which greatly restrict its broad applications in cancer therapy. Phototherapy that uses external light to trigger the therapeutic process holds advantages including high selectivity and efficiency, and low side effects. Recently, it has been proven to be able to stimulate immune response in the tumor region by inducing immunogenic cell death (ICD), the process of which was termed photo-immunotherapy, dramatically improving therapeutic specificity over conventional immunotherapy in several aspects. Among numerous optical materials for photo-immunotherapy, semiconducting polymer nanoparticles (SPNs) have gained more and more attention owing to their excellent optical properties and good biocompatibility. In this review, we summarize recent developments of SPNs for immunotherapy and imaging of immunoactivation. Different therapeutic modalities triggered by SPNs including photo-immunotherapy and photo-immunometabolic therapy are first introduced. Then, applications of SPNs for real-time monitoring immunoactivation are discussed. Finally, the conclusion and future perspectives of this research field are given.

Semiconducting polymer nanoparticles for NIR-II fluorescence imaging-guided photothermal/thermodynamic combination therapy.

Photothermal therapy is a promising phototherapeutic modality that has been widely studied in cancer therapy. However, because of the influence of heat shock protein (HSP), the therapeutic efficacy of photothermal therapy (PTT) is significantly suppressed. To improve the therapeutic efficacy, different tumor-specific therapeutic modalities have been chosen to combine with PTT. However, most of them rely on endogenous stimuli to trigger combination therapy, which may suffer from the issue of incomplete activation. Herein, we develop a PTT/thermodynamic combination therapeutic nanosystem whose therapeutic process is controlled by an external stimulus, near-infrared (NIR) light. The nanosystem (ADPPTN) is composed of a second NIR (NIR-II) fluorescent semiconducting polymer (SP) (DPPT) as the core, and a carboxyl group-decorated amphiphilic copolymer (PSMA-PEG) as the shell with an azo-containing compound (AIPH) loaded via electrostatic interaction. Under 808 nm laser irradiation, DPPT can generate heat to conduct PTT, while the elevated temperature may further trigger the release of AIPH radicals, conducting thermodynamic therapy (TDT). In addition, the NIR-II fluorescence signal emitted from DPPT can light the tumor. Compared with the nanoparticles without AIPH (DPPTN), ADPPTN has better anticancer efficacy under laser irradiation both in vitro and in vivo. Thus, our study provides an NIR-II fluorescence imaging-guided PTT/TDT combination therapeutic nanosystem for efficient cancer theranostics.

Peptide-based semiconducting polymer nanoparticles for osteosarcoma-targeted NIR-II fluorescence/NIR-I photoacoustic dual-model imaging and photothermal/photodynamic therapies.

BACKGROUND: The overall survival rate of osteosarcoma (OS) patients has not been improved for 30 years, and the diagnosis and treatment of OS is still a critical issue. To improve OS treatment and prognosis, novel kinds of theranostic modalities are required. Molecular optical imaging and phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT), are promising strategies for cancer theranostics that exhibit high imaging sensitivity as well as favorable therapeutic efficacy with minimal side effect. In this study, semiconducting polymer nanoparticles (SPN-PT) for OS-targeted PTT/PDT are designed and prepared, using a semiconducting polymer (PCPDTBT), providing fluorescent emission in the second near-infrared window (NIR-II, 1000 - 1700 nm) and photoacoustic (PA) signal in the first near-infrared window (NIR-I, 650 - 900 nm), served as the photosensitizer, and a polyethylene glycolylated (PEGylated) peptide PT, providing targeting ability to OS. RESULTS: The results showed that SPN-PT nanoparticles significantly accelerated OS-specific cellular uptake and enhanced therapeutic efficiency of PTT and PDT effects in OS cell lines and xenograft mouse models. SPN-PT carried out significant anti-tumor activities against OS both in vitro and in vivo. CONCLUSIONS: Peptide-based semiconducting polymer nanoparticles permit efficient NIR-II fluorescence/NIR-I PA dual-modal imaging and targeted PTT/PDT for OS.

Electron-acceptor density adjustments for preparation conjugated polymers with NIR-II absorption and brighter NIR-II fluorescence and 1064 nm active photothermal/gas therapy.

Designing conjugated polymers (CPs) with both efficient second near-infrared wavelength (NIR-II) fluorescence and NIR-II photothermal therapy performance remains a huge challenge, as the introduction of excessively strong electron donor and acceptor units significantly increase non-radiative decay. Herein, we describe an "electron acceptor density adjustment" strategy to address this problem, since a lower electron acceptor density in the conjugated polymer backbone can enhance the radiative rate constant and improve NIR-II fluorescence brightness. We used quaterthiophene (4T) with four repeated thiophene chain units and bithiophene (2 TC) modified with long alkyl side chains to reduce the electron acceptor density in the conjugated polymer backbone. The resultant 1064 nm absorption polymer, TTQ-2TC-4T displayed approximately 7.30-folds enhancement in NIR-II emission intensity compared to that of undoped TTQ-1T at the same mass concentration in toluene solution. Furthermore nanoparticles (TTQ-MnCO NPs) based on TTQ-2TC-4T and CO donors (Mn2(CO)10) were developed to realize NIR-II FI-guided 1064 nm laser-triggered NIR-II PTT/Gas synergistic therapy. The TTQ-MnCO NPs nanoparticles exhibited high photothermal conversion efficiency (η) of 44.43% at 1064 nm and high specific NIR-II fluorescence imaging of the cerebral vasculature of live mice. The in vivo results demonstrate that TTQ-MnCO NPs nanoparticles have excellent PTT/Gas synergistic therapeutic effects in MCF-7 tumor-bearing mice under 1064 nm laser irradiation. This study provides a new approach for optimizing both NIR-II fluorescence and NIR-II photothermal performance of NIR-II absorption conjugated polymers.

Near-infrared-II light excitation thermosensitive liposomes for photoacoustic imaging-guided enhanced photothermal-chemo synergistic tumor therapy.

Despite the great success of photothermal therapy (PTT), it still suffers from many obstacles, such as the limited penetration depth of light, thermoresistance of tumors, and limitations of mono-therapeutic modalities. Herein, second near-infrared (NIR-II, 1064 nm) light excitation thermosensitive liposomes (DG@TLs) were fabricated for photoacoustic imaging (PAI) guided enhanced PTT-chemotherapy. DG@TLs were constructed by encapsulating NIR-II light excitation semiconducting polymers into liposomes composed of phase change materials (PCMs), along with gambogic acid (GA) with chemotherapeutic and heat shock protein inhibition effects. Under 1064 nm laser irradiation, DG@TLs exhibited superior NIR-II PAI and PTT performances with deep tissue penetration while triggering the thermoresponsive release of GA based on the phase transition of PCMs from solid to liquid. The released GA could enhance the NIR-II PTT efficacy by inhibiting the activity of HSP90, reducing the thermoresistance of tumors, exhibiting significant chemotherapeutic effects, and achieving synergistic anti-tumor efficiency. This work provides a new strategy for achieving on-demand drug release and effective theranostics in deep-seated tumor regions.

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.

NIR-II Excitation Phototheranostic Nanomedicine for Fluorescence/Photoacoustic Tumor Imaging and Targeted Photothermal-Photonic Thermodynamic Therapy.

The success of phototheranostics is hampered by some intrinsic defects, such as limited light penetration depth, heat resistance of tumor cells to photothermal therapy (PTT) induced by heat shock protein (HSP) and stress resistance against photodynamic therapy (PDT) caused by hypoxia microenvironment of tumor. Herein, a second near infrared (NIR-II) light excitation phototheranostic nanomedicine has been fabricated by integrating the semiconducting polymer, azo compound, and HSP inhibitor into a thermosensitive liposome, followed by modification with targeting aptamer, forming Lip(PTQ/GA/AIPH) for multimodal phototheranostics of triple-negative breast cancer (TNBC). The phototheranostic nanomedicine provides tumor targeting NIR-II fluorescence and photoacoustic dual-modal imaging, as well as NIR-II PTT. The released HSP inhibitor can effectively inhibit the activity of HSP for enhanced NIR-II PTT. Moreover, azo compound can be decomposed by the NIR-II photothermal activation, generating cytotoxic free radicals and realizing oxygen-irrelevant photonic thermodynamic therapy (PTDT) effects. Under the NIR-II laser irradiation, NIR-II fluorescence/photoacoustic dual-modal imaging guided enhanced NIR-II PTT and PTDT by Lip(PTQ/GA/AIPH), can achieve precise diagnosis and effective suppression of deep-seated TNBC with negligible side effects. This work develops a promising NIR-II excitation phototheranostic nanomedicine for spatiotemporally specific diagnosis and combination therapy of TNBC.