ABSTRACT
As a monumental breakthrough in cancer treatment, immunotherapy has attracted tremendous attention in recent years. However, one challenge faced by immunotherapy is the low response rate and the immune-related adverse events (irAEs). Therefore, it is important to explore new therapeutic strategies and platforms for boosting therapeutic benefits and decreasing the side effects of immunotherapy. In recent years, semiconducting polymer (SP), a category of organic materials with π-conjugated aromatic backbone, has been attracting considerable attention because of their outstanding characteristics such as excellent photophysical features, good biosafety, adjustable chemical flexibility, easy fabrication, and high stability. With these distinct advantages, SP is extensively explored for bioimaging and photo- or ultrasound-activated tumor therapy. Here, the recent advancements in SP-based nanomedicines are summarized for enhanced tumor immunotherapy. According to the photophysical properties of SPs, the cancer immunotherapies enabled by SPs with the photothermal, photodynamic, or sonodynamic functions are highlighted in detail, with a particular focus on the construction of combination immunotherapy and activatable nanoplatforms to maximize the benefits of cancer immunotherapy. Herein, new guidance and comprehensive insights are provided for the design of SPs with desired photophysical properties to realize maximized effectiveness of required biomedical applications.
Subject(s)
Nanoparticles , Neoplasms , Humans , Phototherapy , Nanoparticles/chemistry , Polymers/chemistry , Neoplasms/drug therapy , ImmunotherapyABSTRACT
Theranostic agents with fluorescence in the second near-infrared (NIR-II) window, especially in its long-wavelength region, and NIR-II-excitable photothermal effect is promising but challenging in tumor diagnosis and therapy. Here, we report a simple but effective strategy to develop semiconducting polymer nanoparticles-based theranostic agents (PBQx NPs) and demonstrate their applications for long-wavelength NIR-II fluorescence imaging beyond 1400 nm and photothermal therapy (PTT) of tumors upon excitation at 1064 nm. Both experimental results and theory calculations show that the brightness and photothermal performance of PBQx NPs can be simultaneously improved by simply increasing the repeating unit number of semiconducting polymers. For example, PBQ45 NPs have 5-fold higher brightness than PBQ5 NPs and 6.7-fold higher photothermal effect (based on PCE × Îµ) than PBQ3 NPs, and exhibit promising applications in long-wavelength NIR-II fluorescence abdomen imaging, image-guided tumor resection, and image-guided PTT. This study demonstrates the effectiveness and importance of repeating unit numbers in regulating the theranostic performance, which has not received enough attention before.
Subject(s)
Nanoparticles , Polymers , Cell Line, Tumor , Optical Imaging , Phototherapy , Theranostic Nanomedicine/methodsABSTRACT
Second near-infrared (NIR-II) window type-I photosensitizers have intrinsic advantages in photodynamic/photothermal therapy (PDT/PTT) of some malignant tumors with deep infiltration, large size, complicated location, and low possibility of surgery/radiotherapy. Herein, three chalcogen-element-based donor-acceptor-type semiconducting polymers (poly[2,2â³-((E)-4,4â³-bis(2-octyldodecyl)-[6,6â³-bithieno[3,2-b]pyrrolylidene]-5,5â³(4H,4â³H)-dione)-alt-2,5-(thiophene)] (PTS), poly[2,2â³-((E)-4,4â³-bis(2-octyldodecyl)-[6,6â³-bithieno[3,2-b]pyrrolylidene]-5,5â³(4H,4â³H)-dione)-alt-2,5-(selenophene)] (PTSe), and poly[2,2â³-((E)-4,4â³-bis(2-octyldodecyl)-[6,6â³-bithieno[3,2-b]pyrrolylidene]-5,5â³(4H,4'H)-dione)-alt-2,5-(tellurophene)] (PTTe)) are synthesized and fully characterized, demonstrating strong absorption in the NIR-II region. Upon adjusting the chalcogen elements, the intramolecular charge-transfer characteristics and the heavy-atom effect are tuned to enhance the intersystem crossing rate, improving the photodynamic effect. Moreover, the energy levels and Gibbs free energies are tuned to facilitate the type-I photodynamic process. As a result, PTTe nanoparticles (NPs) produce superoxide anion radicals (O2 â¢- ) more efficiently and demonstrate higher photothermal conversion efficiency than PTS and PTSe NPs upon NIR-II (1064 nm) laser irradiation, exhibiting unprecedented NIR-II type-I PDT/PTT performance in vitro and in vivo. This work provides ideas for achieving high-performance NIR-II type-I PDT/PTT semiconducting polymers for hypoxic oncotherapy.
Subject(s)
Chalcogens , Nanoparticles , Photochemotherapy , Cell Line, Tumor , Photosensitizing Agents/pharmacology , Phototherapy , Photothermal TherapyABSTRACT
Photoacoustic imaging (PA) in the second near infrared (NIR-II) window presents key advantages for deep tissue imaging owing to reduced light scattering and low background signal from biological structures. Here, a thiadiazoloquinoxaline-based semiconducting polymer (SP) with strong absorption in the NIR-II region is reported. After encapsulation of SP in Pluronic F127 (F127) followed by removal of excess surfactant, a dual functional polymer system named surfactant-stripped semiconductor polymeric micelles (SSS-micelles) are generated with water solubility, storage stability, and high photothermal conversion efficiency, permitting tumor theranostics in a mouse model. SSS-micelles have a wideband absorption in the NIR-II window, allowing for the PA imaging at both 1064 and 1300 nm wavelengths. The PA signal of the SSS-micelles can be detected through 6.5 cm of chicken breast tissue in vitro. In mice or rats, SSS-micelles can be visualized in bladder and intestine overlaid 5 cm (signal to noise ratio, SNR ≈ 17 dB) and 5.8 cm (SNR over 10 dB) chicken breast tissue, respectively. This work demonstrates the SSS-micelles as a nanoplatform for deep tissue theranostics.
Subject(s)
Nanoparticles , Neoplasms , Photoacoustic Techniques , Animals , Mice , Micelles , Nanoparticles/chemistry , Neoplasms/diagnostic imaging , Neoplasms/therapy , Photoacoustic Techniques/methods , Phototherapy , Polymers/chemistry , Precision Medicine , Rats , Surface-Active Agents/chemistryABSTRACT
There is an impending need for the development of carrier-free nanosystems for single laser triggered activation of phototherapy, as such approach can overcome the drawbacks associated with irradiation by two distinct laser sources for avoiding prolonged treatment time and complex treatment protocols. Herein, we developed a self-assembled nanosystem (SCP-CS) consisting of a new semiconducting polymer (SCP) and encapsulated ultrasmall CuS (CS) nanoparticles. The SCP component displays remarkable near infrared (NIR) induced photothermal ability, enhanced reactive oxygen species (ROS) generation, and incredible photoacoustic (PA) signals upon activation by 808 nm laser for phototherapy mediated cancer ablation. The CuS component improves the PA imaging ability of SCP-CS, and also enhances photo-induced chemodynamic efficacy. Attributed to promoted single laser-triggered hyperthermia and enhanced ROS generation, the SCP-CS nanosystem shows effective intracellular uptake and intratumoral accumulation, enhanced tumor suppression with reduced treatment time, and devoid of any noticeable toxicity.
Subject(s)
Hyperthermia, Induced , Nanoparticles , Neoplasms , Humans , Neoplasms/therapy , Phototherapy , PolymersABSTRACT
Semiconducting polymer nanoparticles (SPN) have been emerging as novel functional nano materials for phototherapy which includes PTT (photo-thermal therapy), PDT (photodynamic therapy), and their combination. Therefore, it is important to look into their recent developments and further explorations specifically in cancer treatment. Therefore, the present review describes novel semiconducting polymers at the nanoscale, along with their applications and limitations with a specific emphasis on future perspectives. Special focus is given on emerging and trending semiconducting polymeric nanoparticles in this review based on the research findings that have been published mostly within the last five years.
ABSTRACT
Semiconducting polymers (SPs)-based dual photothermal therapy (PTT) obtained better therapeutic effect than single PTT due to its higher photothermal conversion efficiency. However, most dual PTT need to use two lasers for heat generation, which brings about inconvenience and limitation to the experimental operations. Herein, we report the development of "nanococktail" nanomaterials (DTPR) with 808 nm-activated image-guided dual photothermal properties for optimized cancer therapy. Methods: In this work, we co-encapsulated AIEgens (TPA-BDTO, T) and SPs (PDPPP, P) by using maleimide terminated amphiphilic polymer (DSPE-PEG2000-Mal, D), then further conjugated the targeting ligands (RGD, R) through "click" reaction. Finally, such dual PTT nanococktail (termed as DTPR) was constructed. Results: Once DTPR upon irradiation with 808 nm laser, near-infrared fluorescence from T could be partially converted into thermal energy through fluorescence resonance energy transfer (FRET) between T and P, coupling with the original heat energy generated by the photothermal agent P itself, thus resulting in image-guided dual PTT. The photothermal conversion efficiency of DTPR reached 60.3% (dual PTT), much higher as compared to its inherent photothermal effect of only 31.5% (single PTT), which was further proved by the more severe photothermal ablation in vitro and in vivo upon 808 nm laser irradiation. Conclusion: Such smart "nanococktail" nanomaterials could be recognized as a promising photothermal nanotheranostics for image-guided cancer treatment.
Subject(s)
Fluorescence Resonance Energy Transfer/instrumentation , Photothermal Therapy/methods , Theranostic Nanomedicine/methods , Animals , Cell Line, Tumor/drug effects , Cell Line, Tumor/metabolism , Cell Line, Tumor/radiation effects , Drug Delivery Systems/methods , Fluorescence , Hyperthermia, Induced/methods , Lasers , Ligands , Mice , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Polymers , SemiconductorsABSTRACT
Phototherapies including photothermal therapy (PTT) and photodynamic therapy (PDT) have emerged as one of the avant-garde strategies for cancer treatment. Photoacoustic (PA) imaging is a new hybrid imaging modality that shows great promise for real-time in vivo monitoring of biological processes with deep tissue penetration and high spatial resolution. To enhance therapeutic efficacy, reduce side effects and minimize the probability of over-medication, it is necessary to use imaging and diagnostic methods to identify the ideal therapeutic window and track the therapeutic outcome. With this regard, nanotheranostics with the ability to conduct PA imaging and PTT/PDT are emerging. This review summarizes the recent progress of organic nanomaterials including nearinfrared (NIR) dyes and semiconducting polymer nanoparticles (SPNs) in PA imaging guided cancer phototherapy, and also addresses their present challenges and potential in clinical applications.
Subject(s)
Neoplasms/diagnosis , Neoplasms/therapy , Photoacoustic Techniques/methods , Phototherapy/methods , Theranostic Nanomedicine/methods , Animals , Coloring Agents/chemistry , Coloring Agents/therapeutic use , Humans , Hyperthermia, Induced/instrumentation , Hyperthermia, Induced/methods , Nanostructures/chemistry , Nanostructures/therapeutic use , Photoacoustic Techniques/instrumentation , Phototherapy/instrumentation , Polymers/chemistry , Polymers/therapeutic use , Theranostic Nanomedicine/instrumentationABSTRACT
Tumor-specific phototheranostics is conducive to realizing precise cancer therapy. Herein, a novel tumor microenvironment (TME)-responsive phototheranostic paradigm based on the combination of semiconducting polymer brushes and polyoxometalate clusters (SPB@POM) is rationally designed. The acidic TME could drive the self-assembly of SPB@POM into bigger aggregates for enhanced tumor retention and accumulation, while the reducing TME could significantly enhance the NIR absorption of SPB@POM for significant improvement of photoacoustic imaging contrast and photothermal therapy efficacy. Therefore, the smart pH/glutathione (GSH)-responsive SPB@POM allows for remarkable phototheranostic enhancement under the unique TME, which has potential for precise tumor-specific phototheranostics with minimal side effects.