Naturally sourced amphiphilic peptides as paclitaxel vehicles for breast cancer treatment.

The marketed paclitaxel (PTX) formulation Taxol relies on the application of Cremophor EL as a solubilizer. The major drawback of Taxol is its hypersensitivity reactions and a pretreatment of anti-allergic drugs is a necessity. Therefore, developing an efficient and safe delivery vehicle is a solution to increase PTX treatment outcomes with minimal adverse effects. In this work, we prepared the amphiphilic peptides (termed AmP) from soybean proteins using a facile two-step method. AmP could efficiently solubilize PTX by self-assembling into mixed micelles with D-α-tocopherol polyethylene glycol succinate (TPGS), a common pharmaceutical expedient (PTX@TPGS-AmP). The intravenously administrated PTX@TPGS-AmP exhibited a slow clearance (0.24 mL·(min·kg)-1) and an enhanced AUC (41.4 µg.h/mL), manifesting a 3.6-fold increase compared to Taxol. In a murine 4T1 tumor model, PTX@TPGS-AmP displayed a superior antitumor effect over Taxol. Importantly, safety assessment showed a high biocompatibility of AmP and an i.v. dose up to 2500 mg/kg led to no observable abnormalities in the mice. In summary, the AmP presents a new green and easily-prepared amphiphilic biomaterial, with promising potential as a pharmaceutical excipient for drug delivery.

Oral pectin/oligochitosan microspheres for colon-specific controlled release of quercetin to treat inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic, life quality-reducing disease with no cures available yet. To develop an effective medication suitable for long-term use is an urgent but unmet need. Quercetin (QT) is a natural dietary flavonoid with good safety and multifaceted pharmacological activities against inflammation. However, orally administrated quercetin yields unproductive outcomes for IBD treatment because of its poor solubility and extensive metabolism in the gastrointestinal tract. In this work, a colon-targeted QT delivery system (termed COS-CaP-QT) was developed, of which the pectin (PEC)/Ca2+ microspheres were prepared and then crosslinked by oligochitosan (COS). The drug release profile of COS-CaP-QT was pH-dependent and colon microenvironment-responsive, and COS-CaP-QT showed preferential distribution in the colon. The mechanism study showed that QT triggered the Notch pathway to regulate the proliferation of T helper 2 (Th2) cells and group 3 innate lymphoid cells (ILC3s) and the inflammatory microenvironment was remodeled. The in vivo therapeutic results revealed that COS-CaP-QT could relieve the colitis symptoms and maintain the colon length and intestinal barrier integrity.

Magnetism-mediated targeting hyperthermia-immunotherapy in "cold" tumor with CSF1R inhibitor.

Background: Immunotherapy has profoundly changed the landscape of cancer management and represented the most significant breakthrough. Yet, it is a formidable challenge that the majority of cancers - the so-called "cold" tumors - poorly respond to immunotherapy. To find a general immunoregulatory modality that can be applied to a broad spectrum of cancers is an urgent need. Methods: Magnetic hyperthermia (MHT) possesses promise in cancer therapy. We develop a safe and effective therapeutic strategy by using magnetism-mediated targeting MHT-immunotherapy in "cold" colon cancer. A magnetic liposomal system modified with cell-penetrating TAT peptide was developed for targeted delivery of a CSF1R inhibitor (BLZ945), which can block the CSF1-CSF1R pathway and reduce M2 macrophages. The targeted delivery strategy is characterized by its magnetic navigation and TAT-promoting intratumoral penetration. Results: The liposomes (termed TAT-BLZmlips) can induce ICD and cause excessive CRT exposure on the cell surface, which transmits an "eat-me" signal to DCs to elicit immunity. The combination of MHT and BLZ945 can repolarize M2 macrophages in the tumor microenvironment to relieve immunosuppression, normalize the tumor blood vessels, and promote T-lymphocyte infiltration. The antitumor effector CD8+ T cells were increased after treatment. Conclusion: This work demonstrated that TAT-BLZmlips with magnetic navigation and MHT can remodel tumor microenvironment and activate immune responses and memory, thus inhibiting tumor growth and recurrence.

Curcumin/sunitinib co-loaded BSA-stabilized SPIOs for synergistic combination therapy for breast cancer.

Coating supermagnetic iron oxide nanoparticles (SPIOs) with albumin would not only improve their in vivo stability but also improve their drug loading capacity, but current methods are either inefficient or time consuming. Herein, a single step synthesis of bovine serum albumin (BSA)-stabilized SPIOs with high dispersity and stability via a modified co-precipitation method is reported. The benefits of albumin for coating of SPIOs, i.e. its long circulation life, low immunogenicity and drug binding ability to specific binding domains, were all retained in our mildly modified BSA. The BSA-SPIOs thus prepared displayed an excellent T2 contrast enhancing effect and drug loading capacity. Two cytotoxic drugs curcumin and sunitinib, where the former is a drug-resistance depressor and the latter is a tyrosine kinase inhibitor, were further co-loaded into the BSA-SPIOs (denoted SPIO-SC) to achieve combined synergistic therapy. SPIO-SC formulations displayed the most significant tumor inhibition yet least drug-induced toxicity both in vitro and in vivo when compared with free drug formulations. Through in vivo pharmacokinetic analysis, it was demonstrated that SPIO-SC most efficiently delivered the encapsulated drugs to the tumor site, and at the same time maintained the originally designed, optimal ratios of curcumin to sunitinib concentrations at the tumor target and yielded the most optimal synergistic effect and, subsequently, the more effective therapeutic outcomes. The prepared BSA-SPIOs are an extremely promising candidate for both MR imaging and drug delivery as a healthcare material.