pH and Thermal Dual-Sensitive Nanoparticle-Mediated Synergistic Antitumor Effect of Immunotherapy and Microwave Thermotherapy

Abstract

Cationic anticancer peptides, which can induce tumor cell immunogenic death and further promote systemic tumor-specific immune responses, have offered a promising solution to relieve the tumor immunosuppressive microenvironment. However, peptide drugs are easily degraded and lack of targeting ability when administered systemically, leading to limitations in their applications. Herein, we report a pH and thermal dual-sensitive bovine lactoferricin-loaded (one of the most widely studied cationic anticancer peptides) nanoparticles, which simultaneously exhibited antitumor and immune cell activated effects when applied with microwave thermotherapy, an auxiliary method of immunotherapy. The bovine lactoferricin could be delivered to the tumor site by nanoparticles, be immediately released from nanoparticles in the acidic environment of lysosomes and the thermal condition caused by microwave radiation, and ultimately induce tumor apoptosis with the release of damage-associated molecular patterns (DAMPs). It is worth noting that the strategy of bovine lactoferricin-loaded nanoparticles intravenous injection combined with local microwave thermotherapy not only showed excellent efficacy in relieving tumor growth but also resulted in strong antitumor immunities, which was due to the released bovine lactoferricin under stimulating conditions, and the pool of tumor-associated antigens generated by tumor destruction. In conclusion, this work presents a strategy for tumor treatment based on dual-sensitive bovine lactoferricin-loaded nanoparticles combined with microwave thermotherapy, which may provide a solution for cationic anticancer peptides delivery and improving antitumor immune responses.

Treatment of MRSA-infected osteomyelitis using bacterial capturing, magnetically targeted composites with microwave-assisted bacterial killing

“…Compared to solar light, microwave (MV), as an electromagnetic spectrum, has deep penetration ability, high microwaveocaloric therapy (MCT) efficiency, and negligible side effects, which make it a promising candidate in clinical settings 13 – 15 . In particular, the MCT was enhanced by adjusting the impedance matching and attenuation constant between magnetic and dielectric materials of microwaveocaloric sensitivity agents, which can absorb MV energy and convert it into thermal energy.…”

Refining the Design of Diblock Elastin-Like Polypeptides for Self-Assembly into Nanoparticles

“…UCST-polymers in aqueous medium (e.g., poly( N -acryloylglycinamide), poly(acrylamide- co -acrylonitrile), polybetaine) are much less reported than LCST-polymers but have aroused a great interest in the last decade [ 2 , 3 , 8 ]. Polymers exhibiting a UCST have been studied for the development of drug delivery systems to release therapeutics under hyperthermic conditions [ 9 ]. In contrast, LCST-polymers come in a wider variety and comprise synthetic polymers such as poly( N -isopropylacrylamide) (PNIPAM) [ 10 ], the most extensively studied LCST-polymer, but also poly(oligo ethylene glycol methacrylate) (P(OEGMA)) [ 11 ], poly(2-oxazoline) (POx) [ 12 ], polypeptoids [ 13 ], poly(N-vinylcaprolactam) [ 14 ] and certain block copolymers [ 15 , 16 ].…”

Synergistic effect of tumor chemo-immunotherapy induced by leukocyte-hitchhiking thermal-sensitive micelles

“…7,8 Subsequently, the activation of T cells leads to the recruitment of cytotoxic T cells (CTLs) to the tumor site, thereby promoting tumor-speci c cellular immunity, which can further enhance antitumor effects of chemotherapeutic agents. 9,10 Despite the ICD induction and immune response initiation of these select chemotherapeutic drugs, there remain challenges. Tumor cells can release large amounts of ATP during ICD induced by chemotherapeutic drugs, which is subsequently metabolized to adenosine (ADO, a potent immunosuppressor) by ectonucleotidases, such as CD39 and CD73.…”

“…Smart nanoparticle drug delivery system is an effective way to alter biodistribution of drugs and achieve spatiotemporally controlled drug release, which is bene cial for improving treatment safety and e cacy. 9,[22][23][24] Signi cantly, thermal-sensitive drug delivery system has attracted much attention; hyperthermia stimuli at the tumor site can accelerate the drug release from nanoparticles to achieve precise therapy, and on the other hand, hyperthermia itself can also suppress tumor growth. 25,26 Despite these advantages, delivering nanoparticle platforms in patients with advanced forms of cancer remains a challenge.…”