Biomimetic, pH-Responsive Nanoplatforms for Cancer Multimodal Imaging and Photothermal Immunotherapy

Abstract

Photothermal therapy (PTT), by converting light to thermal energy, has become a novel and noninvasive technique for tumor thermal ablation in clinical practice. However, as a result of phagocytosis of reticuloendothelial cells, current photothermal agents (PTAs) derived from exogenous materials suffer from incompetent tumor targeting and brief internal circulation time. The resulting poor accumulation of PTAs in the target area severely reduces the efficacy of PTT. In addition, the potential toxicity of PTAs, excessive laser exposure, and possibilities of tumor recurrence and metastasis following PTT are still intractable problems that severely influence patients' quality of life. Herein, a biomimetic pH-responsive nanoprobe was prepared via cancer cell membrane coating polydopamine (PDA)−CaCO 3 nanoparticles (CPCaNPs) for photoacoustic (PA)/ultrasonic (US)/thermal imaging-guided PTT. When CPCaNPs targeted and infiltrated into the tumor's acidic microenvironment, the decomposed CO 2 bubbles from homologous targeting CPCaNPs enhanced ultrasonic (US) signals obviously. At the same time, the PDA of CPCaNPs not only performed efficient PTT of primary tumors but also generated photoacoustic (PA) signals. In addition, an immune checkpoint pathway blockade was combined, which inhibited tumor recurrence and metastasis significantly and improved the immunosuppressive microenvironment after PTT to a large extent. Thus, these proposed biomimetic pH-responsive CPCaNPs provide a promising strategy for precise PTT immunotherapy under the intelligent guidance of PA/US/thermal imaging and show great potential for clinical translation.

Calcium Carbonate-Based Nanoplatforms for Cancer Therapeutics: Current State of Art and Future Breakthroughs

“…It is often challenging to completely eradicate tumors using a single method, and employing multiple modes of therapy can effectively destroy the tumor while reducing side effects. , CBN can be used for multimodal cancer therapy (Table ), including chemodynamic therapy (CDT), RT, PTT, PDT, sonodynamic therapy (SDT), chemotherapy, immunotherapy, starvation therapy, and gas therapy. ,, Due to their excellent drug-loading capability, CBN are well-suited for multimode cancer treatment. External stimulation can activate cell stress reactions (CSR), which counteract the antitumor effect.…”

“…Effects on Tumor Microenvironment. Besides drug loading, CBN also plays several important roles in TME modulation, such as providing CO 2 , 58 adjusting pH, 71 and serving as a Ca 2+ supercarrier, 72 which induces immunogenic cell death (ICD) and autophagy thereby activating immunotherapy.…”

“…Due to the acoustic properties of CO 2 bubbles, they can serve as a good ultrasound contrast agent, providing a novel diagnostic method for tumor treatment . For instance, to implement photoacoustic (PA), ultrasound, and thermal imaging guided PTT, Wan et al prepared biomimetic pH-responsive nanoprobes using tumor cell membrane-modified polydopamine (PDA)-CaCO 3 NPs (CPCaNPs) . Once the CPCaNPs targeted and penetrated deep into the acidic TME, the CO 2 bubbles generated by the decomposition of CPCaNPs significantly enhanced the US signal.…”

Cell membrane coated nanoparticles as a biomimetic drug delivery platform for enhancing cancer immunotherapy

“…These NPs exhibited concentration-dependent heating ability with a 36.7% photothermal conversion efficiency and enabled photoacoustic (PA) imaging. 142 Many other photosensitizers have been incorporated into CMNPs to exert photothermal effects, including indocyanine green (ICG), IR-797, etc. For instance, ICG was loaded into Fe 3 O 4 coated with hybrid cell membranes (erythrocyte and ID8 cell membranes), achieving a desirable photothermal effect.…”

PEI-Based Nanoparticles for Tumor Immunotherapy via In Situ Antigen-Capture Triggered by Photothermal Therapy

“…Several cancer vaccines based on neoantigens have been shown to be safe and effective in clinical studies. − Cancer vaccines combined with immune checkpoint inhibitors (ICIs), including programmed death-1 (PD-1) receptors and CTLA-4 (cytotoxic T-lymphocyte-associated antigen 4), bring hope to reversing “cold tumors” that are resistant to conventional immunotherapies. ,, Traditional strategies of treating tumors (such as radiotherapy, chemotherapy, − photothermal therapy, etc.) can cause tumor cells to undergo immunogenic cell death (ICD), leading to in situ production of tumor antigens and damage-associated molecular patterns (DAMPs) such as calreticulin (CRT), − which may induce tumor-specific immune response. − However, most tumor antigens are very low in quantity, structurally diverse, prone to degradation, and only weakly immunogenic, therefore not sufficient to activate the immune system …”