A size/charge/targeting changeable nano-booster to realize synergistic photodynamic-immunotherapy with high safety

Zang, Jie; He, Ruiqing; Liu, Y.; Su, Runping; Zhao, Yuge; Zheng, Xiao; Liu, Ying; Chong, Gaowei; Ruan, Shuangrong; Wang, Huaiji; Xu, Dailin; Dong, Haiqing; Li, Yongyong

doi:10.1016/j.cej.2022.134585

Cited by 15 publications

(31 citation statements)

References 37 publications

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“…Zhang et al have produced a systematic description of functional components of platelet membrane vesicles required for cardiovascular therapeutic purposes [ 11 ]. In our work, we developed an AMI environment responsive PBA nanocarrier, adjusted from our previous work, designed to disintegrate under slightly acidic conditions and release tPA for thrombolysis [ 10 ]. PBA nanoparticles were coated with platelet membrane by extrusion in order to confer thrombus-targeting properties.…”

Section: Discussionmentioning

confidence: 99%

“…pH-responsive tPA nanoparticles (TPN) were synthesized as described in our previous work [ 10 ]. Briefly, PEI–PBA was achieved by reacting 38.5 mg of PBA, 50 mg of PEI and acid-binding agent trimethylamine in 2 mL of DMSO at 70 °C for 24 h followed by dialysis and lyophilization.…”

Section: Methodsmentioning

confidence: 99%

“…PTPN consists of three components (Fig. 1 a): a thrombus-targeting platelet-derived outer membrane and a core containing a pH-responsive phenylboronic acid modified branched polyethyleneimine (PEI–PBA) and protocatechualdehyde (PC) conjugated tPA [ 10 ]. Platelet membranes have thrombus-targeting activity due to their content of immunoregulatory proteins and glycoprotein integrins, such as CD42, CD61, and GPIIb/IIIa, which interact with damaged vascular endothelial cells and fibrin [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

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Thrombus-specific/responsive biomimetic nanomedicine for spatiotemporal thrombolysis and alleviation of myocardial ischemia/reperfusion injury

et al. 2022

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Acute myocardial infarction (AMI) is usually caused by coronary thrombosis. However, the short half-life, lack of targetability and inevitable ischemia/reperfusion injury secondary to revascularization, which characterizes tissue plasminogen activator (tPA) limit its thrombolytic efficacy for AMI. To address the targeted and site-specific delivery of tPA, the current study reports the construction of a thrombus-targeting and responsive biomimetic nanoparticle (PTPN) for spatiotemporal treatment of AMI. PTPN was constituted by the thrombus microenvironment- responsive phenylboronic acid (PBA) nanocarrier, antioxidant molecular protocatechualdehyde (PC) and tPA with thrombolytic effect, which were enclosed by the platelet membrane. The thrombus-targeting capability of the platelet membrane enabled the adhesion of PTPN to damaged endothelial cells. The nanoparticle disintegrated under slightly acid condition and re-opened the infarct-related artery during the period of ischemia. Sequentially, ROS induced by blood reperfusion was eliminated by PC released from particle disintegration, and the cardiomyocyte mitochondrial function was protected from reperfusion injury. Therefore, this thrombus-specific/responsive biomimetic nanomedicine provides a spatiotemporal paradigm for AMI treatment with promising clinical translation prospects.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Thrombus-specific/responsive biomimetic nanomedicine for spatiotemporal thrombolysis and alleviation of myocardial ischemia/reperfusion injury

et al. 2022

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“…The acid-responsive nanocomplex can be converted into smaller nanoparticles (~28 nm) with a cationic charge in the weakly acidic TME that favours enhanced tumour penetration of aPDL1 and Ce6. This combination increased intratumoral infiltration of different immune cells, especially CD8 + T lymphocytes, when evaluated using melanoma and breast cancer induced mice models [ 22 ]. Along similar lines, modulation of the macrophage polarisation was attempted using a self-assembled nanoparticle (PyroR) formed by the combination of the photosensitizer pyropheophorbide-a (Pyro) for photostimuli-responsive cytotoxicity and the TLR agonist resiquimod (R848) for altering polarisation ( Figure 3 ).…”

Section: Modulation Of Tumour Immunity Using Nanoparticlesmentioning

confidence: 99%

Emerging Trends in Nano-Driven Immunotherapy for Treatment of Cancer

2023

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Despite advancements in the development of anticancer medications and therapies, cancer still has the greatest fatality rate due to a dismal prognosis. Traditional cancer therapies include chemotherapy, radiotherapy, and targeted therapy. The conventional treatments have a number of shortcomings, such as a lack of selectivity, non-specific cytotoxicity, suboptimal drug delivery to tumour locations, and multi-drug resistance, which results in a less potent/ineffective therapeutic outcome. Cancer immunotherapy is an emerging and promising strategy to elicit a pronounced immune response against cancer. Immunotherapy stimulates the immune system with cancer-specific antigens or immune checkpoint inhibitors to overcome the immune suppressive tumour microenvironment and kill the cancer cells. However, delivery of the antigen or immune checkpoint inhibitors and activation of the immune response need to circumvent the issues pertaining to short lifetimes and effect times, as well as adverse effects associated with off-targeting, suboptimal, or hyperactivation of the immune system. Additional challenges posed by the tumour suppressive microenvironment are less tumour immunogenicity and the inhibition of effector T cells. The evolution of nanotechnology in recent years has paved the way for improving treatment efficacy by facilitating site-specific and sustained delivery of the therapeutic moiety to elicit a robust immune response. The amenability of nanoparticles towards surface functionalization and tuneable physicochemical properties, size, shape, and surfaces charge have been successfully harnessed for immunotherapy, as well as combination therapy, against cancer. In this review, we have summarized the recent advancements made in choosing different nanomaterial combinations and their modifications made to enable their interaction with different molecular and cellular targets for efficient immunotherapy. This review also highlights recent trends in immunotherapy strategies to be used independently, as well as in combination, for the destruction of cancer cells, as well as prevent metastasis and recurrence.

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“…Increasing physical and other chemical interactions and chemical cross-linking can efficiently improve the stability of nanodrugs in vivo. − On the other hand, the more sensitive transition of stability and affinity of nanodrugs can increase tumor accumulation, internalization, and release in the TME after tuning their characteristics of size, zeta potential, and hydrophilicity. − Thus, it is vital to develop an effective polypeptide-based nanocarrier by integrating high stability in the circulation with high sensitivity in the TME through adjusting the surface charge and increasing the polarity contrast between the hydrophobic core and zwitterionic shells. Biguanides, such as metformin or phenformin that is used for treating diabetes, have shown an antitumor activity by disrupting cell metabolism and decreasing energy supply. , Phenformin (Phen) is a positively charged one with more hydrophobicity and higher antitumor potency than metformin. , Thus, encapsulation of phenformin in the negative chemotherapeutic SMD-conjugated zwitterionic polypeptides can tune the zeta potential to sensitize the nanodrug to environmental changes and stabilize the nanodrug in circulation.…”

Section: Introductionmentioning

confidence: 99%

Enhancing the Antitumor Efficacy of Zwitterionic Peptide-Based Nanoscale Micelles through Sensitizing Their Response in Solid Tumors

Wei

Xiang

Xue

et al. 2022

ACS Appl. Nano Mater.

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Although nanodelivery has made unprecedented progress in enhancing the efficacy of chemotherapeutic drugs, there is still much room for improvement. Zwitterionic nanodrugs have great potential to be a universal platform for nanodelivery because of the exceptional hemocompatibility and ultralow immunogenicity, although they are sensitive to the tumor microenvironment (TME) for tumor cell targeting and internalization. Here, a negatively biased zwitterionic peptide micelle, a mimic of albumin, was developed to improve two vital factors, which are the responsive transition of stability and affinity to tumor cells from circulation to the slightly acidic TME. The incorporation of positively charged hydrophobic phenformin into the camptothecin (CPT)-conjugated micelles (Pep-SSetc-CPT@Phen) can make the micelles more compact to reduce premature drug release in circulation while improving the sensitivity of the micelles to MCF-7-xenografted tumors by tuning their zeta potential in the TME. Thus, Pep-SSetc-CPT@Phen exhibited more tumor-preferred biodistribution and longer blood circulation than nonphenformin-incorporated micelles (Pep-SSetc-CPT), thereby enhancing tumor growth inhibition with lower side effects. Together, these results have provided a promising combinational method to enhance the transition of stability and the sensitivity to the TME for developing biomimetic zwitterionic nanodrugs with high antitumor efficacy.

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A size/charge/targeting changeable nano-booster to realize synergistic photodynamic-immunotherapy with high safety

Cited by 15 publications

References 37 publications

Thrombus-specific/responsive biomimetic nanomedicine for spatiotemporal thrombolysis and alleviation of myocardial ischemia/reperfusion injury

Thrombus-specific/responsive biomimetic nanomedicine for spatiotemporal thrombolysis and alleviation of myocardial ischemia/reperfusion injury

Emerging Trends in Nano-Driven Immunotherapy for Treatment of Cancer

Enhancing the Antitumor Efficacy of Zwitterionic Peptide-Based Nanoscale Micelles through Sensitizing Their Response in Solid Tumors

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