Biodegradable Polymer with Effective Near‐Infrared‐II Absorption as a Photothermal Agent for Deep Tumor Therapy

Abstract

Based on the clinical needs, the criteria for ideal PTA are shown as follows: 1) good biodegradability, 2) good photostability, 3) strong absorption in the NIR region for tissue penetration, 4) high photothermal conversion efficiency (PCE). [2] Preclinical studies and early phase trials of PTT have demonstrated promising therapeutic efficacy for superficial tumors (e.g., skin, head, and neck cancer); [3] its use for deep tumors (e.g., lung cancer and ovarian cancer), however, is hampered by several key factors, such as effective delivery of PTAs to tumor sites, the biocompatibility of PTAs, adsorption, and conversion of photoenergy through deep tissues. [4] Generally, light with a wavelength in the near-infrared-II window (NIR-II, 1000-1700 nm) could provide a deeper tissue-penetration length (≈ 5 mm) with less scattering and tissue absorption, [5] compared with light in the near-infrared-I window (NIR-I, 650-950 nm) with a tissue penetration depth of less than 1 mm. [6] Developing PTAs with high biocompatibility, adsorption in the NIR-II window, and photoenergy-conversion efficiency, in this context, is essential toward PTT for deep tumors.Current NIR-II PTAs are mainly based on inorganic particles (e.g., gold nanoparticles, copper sulfide, and black phosphorus), [7] which are generally non-degradable under physiological conditions. Despite that some studies have claimed biodegradability for such materials, the degradation mechanisms are unclear, and balancing the degradability and photothermal performance of such materials remains difficult. [8] Organic dyes have also been explored, [9] whereas their poor photostability could limit their use as effective NIR-II PTAs. [10] Conjugated polymer, which affords strong absorption in the NIR-II window and excellent photostability, [6a,11,12] is highly promising PTAs; however, such materials are inherently nondegradable under physiological conditions. [13] Most research in polymeric PTAs has been focused on photothermal performance; little attention was paid to their biodegradability. [14] Herein, we report a novel class of biodegradable polymeric PTAs through incorporating a flexible unit containing disulfide bonds into the conjugated backbones. To distinguish it with traditional conjugated polymer, we name this new type of polymer as "pseudo-conjugated polymers". Disulfide bonds are cleavable by glutathione (GSH), the most abundant thiol in animal cells, of which the concentration in tumor cells is generally 100-1000 times higher than that in normal cells. [15] As illustrated Photothermal therapy holds great promise for cancer treatment due to its effective tumor ablation and minimal invasiveness. Herein a new class of biodegradable photothermal agents with effective adsorption in both nearinfrared-I (NIR-I) and NIR-II windows is reported for deep tumor therapy. As demonstrated in a deep-seated ovarian cancer model, photothermal therapy using 1064 nm irradiation effectively inhibits tumor progression and prolongs survival spans. This work provides a new design ...

Thiadiazoloquinoxaline derivative-based NIR-II organic molecules for NIR-II fluorescence imaging and photothermal therapy

“…For instance, the Xiao group developed a series of biodegradable polymers for cancer treatment. 69,70 Secondly, considering that the radiative decay (FI) and non-radiative decay (PAI and PTT) are competitive, it is crucial to maintain a balance among the two processes. Although the Fan group has provided some strategies, such as molecular engineering, introduction of side chains, weak donor units and acceptors, and reduced electron acceptor density, for the development of conjugated polymers to achieve NIR-II PTT assisted by NIR-II FI, 40,[55][56][57] some strategies based on theoretical mechanisms are still rare.…”

Self‐Sacrificially Degradable Pseudo‐Semiconducting Polymer Nanoparticles that Integrate NIR‐II Fluorescence Bioimaging, Photodynamic Immunotherapy, and Photo‐Activated Chemotherapy

“…[18] Subsequently, monomer 2,6-diiodo-4,4-difluoro-1,3,5,7-tetramethyl-8-phenyl-4-bora-3a,4adiaza-s-indacene (defined as M2) with strong fluorescence and outstanding photostability was designed and synthesized for NIR-II fluorescence bioimaging and singlet oxygen ( 1 O 2 ) generation for PDT (Figures S1 and S2, Supporting Information). To overcome the limitations of non-biodegradability, a reduction-sensitive monomer disulfanediylbis(ethane-2,1-diyl)-bis(5-bromothiophene-2-carboxylate) (defined as M3a) [19] was incorporated into the polymer main chain of PSP, which could ensure the biodegradability of PSP in the tumor site with high levels of GSH (Figure 1A). [20,21] For comparison, butane-1,4diyl bis(5-bromothiophene-2-carboxylate) (defined as M3b) without disulfide bonds was also designed and introduced into a polymer, that is, PSP-C.…”

Electrospun Silk Fibroin/Polylactic-co-glycolic Acid/Black Phosphorus Nanosheets Nanofibrous Membrane with Photothermal Therapy Potential for Cancer

“…PTT, which relies on photothermal properties for converting light irradiation into heat to ablate tumors, has attracted wide attention in recent research in cancer treatment, owing to its non-invasive, local treatment and good therapeutic effects. The preclinical studies and early trials prove that PTT has good therapeutic effects on superficial tumors (e.g., skin cancer, head and neck cancer) [ 47 ].…”