On the basis of the Jablonski diagram, the photophysical properties of optical agents are highly associated with biomedical function and efficacy. Herein, the focus is on organic/polymer optical ...agents and the recent progress in the main strategies for regulating their photophysical properties to achieve superior cancer diagnosis/phototheranostics applications are highlighted. Both the approaches of nanoengineering and molecular design, which can lead to optimized effectiveness of required biomedical function, are discussed.
The main strategies for regulating the photophysical properties of organic/polymer optical agents to achieve superior biomedical applications in cancer diagnosis/phototheranosis are highlighted. The approaches of nanoengineering and molecular design, which can lead to optimized effectiveness of required biomedical function, are discussed.
Herein, we report an activatable near‐infrared (NIR) afterglow theranostic prodrug that circumvents high background noise interference caused by external light excitation. The prodrug can release ...hydroxycamptothecin (HCPT) in response to the high intratumoral peroxynitrite level associated with immunogenic cell death (ICD), and synchronously activate afterglow signal to monitor the drug release process and cold‐to‐hot tumor transformation. The prodrug itself is an ICD inducer achieved by photodynamic therapy (PDT). PDT initiates ICD and recruits first‐arrived neutrophils to secrete peroxynitrite to trigger HCPT release. Intriguingly, we demonstrate that HCPT can significantly amplify PDT‐mediated ICD process. The prodrug thus shows a self‐sustainable ICD magnification effect by establishing an “ICD‐HCPT release‐amplified ICD” cycling loop. In vivo studies demonstrate that the prodrug can eradicate existing tumors and prevent further tumor recurrence through antitumor immune response.
We report a theranostic prodrug that could self‐report the drug release, immunogenic cell death (ICD) progression, and cold‐to‐hot tumor transformation with activated near‐infrared afterglow chemiluminescence. Such an intelligent prodrug also shows a unique self‐sustainable ICD magnification effect, completely eradicating the existing tumor and preventing further tumor recurrence through enhanced antitumor immune response.
Planar donor and acceptor (D–A) conjugated structures are generally believed to be the standard for architecting highly efficient photothermal theranostic agents, in order to restrict intramolecular ...motions in aggregates (nanoparticles). However, other channels of extra nonradiative decay may be blocked. Now this challenge is addressed by proposing an “abnormal” strategy based on molecular motion in aggregates. Molecular rotors and bulky alkyl chains are grafted to the central D–A core to lower intermolecular interaction. The enhanced molecular motion favors the formation of a dark twisted intramolecular charge transfer state, whose nonradiative decay enhances the photothermal properties. Result shows that small-molecule NIRb14 with long alkyl chains branched at the second carbon exhibits enhanced photothermal properties compared with NIRb6, with short branched chains, and much higher than NIR6, with short linear chains, and the commercial gold nanorods. Both in vitro and in vivo experiments demonstrate that NIRb14 nanoparticles can be used as nanoagents for photoacoustic imaging-guided photothermal therapy. Moreover, charge reversal poly(β-amino ester) makes NIRb14 specifically accumulate at tumor sites. This study thus provides an excited molecular motion approach toward efficient phototheranostic agents.
The shortened is as follows: Therapeutic gas nitric oxide (NO) has demonstrated the unique advances in biomedical applications due to its prominent role in regulating physiological/pathophysiological ...activities in terms of vasodilation, angiogenesis, chemosensitizing effect, and bactericidal effect. However, it is challenging to deliver NO, due to its short half‐life (<5 s) and short diffusion distances (20–160 µm). To address these, various polymeric NO delivery nanoplatforms (PNODNPs) have been developed for cancer therapy, antimicrobial and cardiovascular therapeutics, because of the important advantages of polymeric delivery nanoplatforms in terms of controlled release of therapeutics and the extremely versatile nature. This reviews highlights the recent significant advances made in PNODNPs for NO storing and targeting delivery. The ideal and unique criteria that are required for PNODNPs for treating cancer, cardiovascular diseases and infection, respectively, are summarized. Hopefully, effective storage and targeted delivery of NO in a controlled manner using PNODNPs could pave the way for NO‐sensitized synergistic therapy in clinical practice for treating the leading death‐causing diseases.
The recent significant advances made in polymeric nitric oxide (NO) delivery nanoplatforms (PNODNPs) for NO storage and targeting delivery are highlighted. The ideal criteria that are required for PNODNPs for treating cancer, cardiovascular diseases, and infection, respectively, are summarized.
Photoacoustic (PA) imaging emerges as a promising technique for biomedical applications. The development of new strategies to boost PA conversion without depressing other properties (e.g., ...fluorescence) is highly desirable for multifunctional imaging but difficult to realize. Here, we report a new phenomenon that active intramolecular motions could promote PA signal by specifically increasing thermal‐to‐acoustic conversion efficiency. The compound with intense intramolecular motion exhibits amplified PA signal by elevating thermal‐to‐acoustic conversion, and the fluorescence also increases due to aggregation‐induced emission signature. The simultaneously high PA and fluorescence brightness of TPA‐TQ3 NPs enable precise image‐guided surgery. The preoperative fluorescence and PA imaging are capable of locating orthotopic breast tumor in a high‐contrast manner, and the intraoperative fluorescence imaging delineates tiny residual tumors. This study highlights a new design guideline of intramolecular motion amplifying PA effect.
A compound with intense intramolecular motions exhibits an amplified photoacoustic signal by specifically elevating the thermal‐to‐acoustic conversion efficiency, and the fluorescence brightness also increases due to the aggregation‐induced emission signature. Precise in vivo image‐guided cancer surgery in different stages is conducted, greatly boosting the surgery outcome.
With the rapid development of materials science, photosensitive materials have been widely used in the field of immunogenic cell death(ICD), which was on account of the reactive oxygen species(ROS) ...generation by photosensitizer under light irradiation inducing cellular oxidative stress during the dying of cells. Considerable researches related to photodynamic therapy(PDT) induced ICD were conducted and exhibited brilliant performance in cancer immunotherapy. Herein, a variety of different strategies for PDT induced ICD have been summarized and discussed to provide researchers more inspiration for cancer immunotherapy.
Semiconducting polymer nanoparticles (SPNs) emitting in the second near-infrared window (NIR-II, 1000–1700 nm) are promising materials for deep-tissue optical imaging in mammals, but the brightness ...is far from satisfactory. Herein, we developed a molecular design strategy to boost the brightness of NIR-II SPNs: structure planarization and twisting. By integration of the strong absorption coefficient inherited from planar π-conjugated units and high solid-state quantum yield (ΦPL) from twisted motifs into one polymer, a rise in brightness was obtained. The resulting pNIR-4 with both twisted and planar structure displayed improved ΦPL and absorption when compared to the planar polymer pNIR-1 and the twisted polymer pNIR-2. Given the emission tail extending into the NIR-IIa region (1300–1400 nm) of the pNIR-4 nanoparticles, NIR-IIa fluorescence imaging of blood vessels with enhanced clarity was observed. Moreover, a pH-responsive poly(β-amino ester) made pNIR-4 specifically accumulate at tumor sites, allowing NIR-IIa fluorescence image-guided cancer precision resection. This study provides a molecular design strategy for developing highly bright fluorophores.
Persistent luminescence without excitation light and tissue autofluorescence interference holds great promise for biological applications, but is limited by available materials with long‐wavelength ...emission and excellent clinical potential. Here, we report that porphyrin derivatives can emit near‐infrared persistent luminescence over 60 min after cessation of excitation light or on interaction with peroxynitrite. A plausible mechanism of the successive oxidation of vinylene bonds was demonstrated. A supramolecular probe with a β‐sheet structure was constructed to enhance the tumor targeting ability and the photoacoustic and persistent luminescence signals. Such probes featuring light‐triggered function transformation from photoacoustic imaging to persistent luminescence imaging permit advanced image‐guided cancer surgery. Furthermore, peroxynitrite‐activated persistent luminescence of the supramolecular probe also enables rapid and precise screening of immunogenic cell death drugs.
Porphyrin derivatives that can emit near‐infrared persistent luminescence (PL) over 60 min are reported and a mechanism for the phenomenon is proposed. The derivatives are used to synthesize supramolecular probes with peroxynitrite‐activated PL and light‐triggered imaging‐modality transformation characteristics that permit improved biological uses.
Axial modified phthalocyanine (BtPc), aiming at avoiding H-aggregation and utilizing long wavelength light, was designed and synthesized. With the aid of polymer nanotechnology, BtPc loaded polymeric ...micelles with strong singlet oxygen generating ability and enhanced photodynamic therapy efficiency were developed. Optical characterizations and in vitro evaluations proved that the BtPc loaded polymeric micelles hold great potential for photodynamic therapy.
Although organic materials with near infrared (NIR)‐II fluorescence and a photothermal effect have been widely investigated for the accurate diagnosis and treatment of tumors, optimizing the output ...signals of both remain challenging. Here, a strategy by “enlarging absorption reservoir” to address this issue, since an increase in photon absorption can naturally enhance output signals, is proposed. As a proof‐of‐concept, a large π‐conjugated diketopyrrolopyrrole (DPP) unit is selected to fabricate strong light‐absorbing systems. To enhance solid‐state fluorescence, highly twisted alkylthiophene–benzobisthiadiazole–alkylthiophene and triphenylamine rotor are introduced to restrict the strong intermolecular π–π interactions. Moreover, the number of DPP units in molecules is engineered to optimize photophysical properties. Results show that TDADT with two DPP units possesses an exceptionally high molar absorptivity of 2.1 × 105 L mol−1 cm−1 at 808 nm, an acceptable NIR‐II quantum yield of 0.1% (emission peak at 1270 nm), and a sizeable photothermal conversion efficiency of 60.4%. The excellent photophysical properties of the TDADT nanoparticles are particularly suitable for in vivo NIR‐II imaging‐guided cancer surgery and NIR‐I photothermal therapy. The presented strategy provides a new approach of designing highly efficient NIR‐II phototheranostic agents.
A molecular design strategy, enlarging the absorption reservoir, is proposed to enhance fluorescence intensity and photothermal properties through an increase in photon absorption. The resulting molecules are particularly suitable for in vivo near infrared (NIR)‐II imaging‐guided cancer surgery and NIR‐I photothermal therapy in live mice.
