Self-assembling paclitaxel-mediated stimulation of tumor-associated macrophages for postoperative treatment of glioblastoma.

The unique cancer-associated immunosuppression in brain, combined with a paucity of infiltrating T cells, contributes to the low response rate and poor treatment outcomes of T cell-based immunotherapy for patients diagnosed with glioblastoma multiforme (GBM). Here, we report on a self-assembling paclitaxel (PTX) filament (PF) hydrogel that stimulates macrophage-mediated immune response for local treatment of recurrent glioblastoma. Our results suggest that aqueous PF solutions containing aCD47 can be directly deposited into the tumor resection cavity, enabling seamless hydrogel filling of the cavity and long-term release of both therapeutics.

Collagen-Binding Peptide-Enabled Supramolecular Hydrogel Design for Improved Organ Adhesion and Sprayable Therapeutic Delivery.

Spraying serves as an attractive, minimally invasive means of administering hydrogels for localized delivery, particularly due to high-throughput deposition of therapeutic depots over an entire target site of uneven surfaces. However, it remains a great challenge to design systems capable of rapid gelation after shear-thinning during spraying and adhering to coated tissues in wet, physiological environments. We report here on the use of a collagen-binding peptide to enable a supramolecular design of a biocompatible, bioadhesive, and sprayable hydrogel for sustained release of therapeutics.

Supramolecular Tubustecan Hydrogel as Chemotherapeutic Carrier to Improve Tumor Penetration and Local Treatment Efficacy.

Local chemotherapy is a clinically proven strategy in treating malignant brain tumors. Its benefits, however, are largely limited by the rapid release and clearance of therapeutic agents and the inability to penetrate through tumor tissues. We report here on a supramolecular tubustecan (TT) hydrogel as both a therapeutic and drug carrier that enables long-term, sustained drug release and improved tumor tissue penetration.

Supramolecular prodrug hydrogelator as an immune booster for checkpoint blocker-based immunotherapy.

Immune checkpoint blockers (ICBs) have shown great promise at harnessing immune system to combat cancer. However, only a fraction of patients can directly benefit from the anti-programmed cell death protein 1 (aPD1) therapy, and the treatment often leads to immune-related adverse effects. In this context, we developed a prodrug hydrogelator for local delivery of ICBs to boost the host's immune system against tumor.

Supramolecular Design of Unsymmetric Reverse Bolaamphiphiles for Cell-Sensitive Hydrogel Degradation and Drug Release.

Self-assembly of peptide-based building units into supramolecular nanostructures creates an important class of biomaterials with robust mechanical properties and improved resistance to premature degradation. Yet, upon aggregation, substrate-enzyme interactions are often compromised because of the limited access of macromolecular proteins to the peptide substrate, leading to either a reduction or loss of responsiveness to biomolecular cues. Reported here is the supramolecular design of unsymmetric reverse bolaamphiphiles (RBA) capable of exposing a matrix metalloproteinase (MMP) substrate on the surface of their filamentous assemblies.

Self-assembling and self-formulating prodrug hydrogelator extends survival in a glioblastoma resection and recurrence model.

Glioblastoma multiforme (GBM) is the most common and devastating type of primary brain cancer. Despite surgery and chemo/radiation therapy, recurrence often takes place and leads to patient death. We report here on the development of a camptothecin (CPT)-based self-assembling prodrug (SAPD) hydrogel that can be used as an adjunct therapy for local treatment of GBM following maximal tumor resection.

Interface-Enrichment-Induced Instability and Drug-Loading-Enhanced Stability in Inhalable Delivery of Supramolecular Filaments.

Filamentous microorganisms traveling in aerosol particles display enhanced deposition and retention in the lungs. Inspired by this shape-related biological effect, we report here on the use of supramolecular filaments as potential inhalable drug carriers within aerosols via jet nebulization. We found that the peptide design and supramolecular stability play a crucial role in the interfacial stability and aerosolization properties of the supramolecular filaments.

Fine-Tuning the Linear Release Rate of Paclitaxel-Bearing Supramolecular Filament Hydrogels through Molecular Engineering.

One key design feature in the development of any local drug delivery system is the controlled release of therapeutic agents over a certain period of time. In this context, we report the characteristic feature of a supramolecular filament hydrogel system that enables a linear and sustainable drug release over the period of several months. Through covalent linkage with a short peptide sequence, we are able to convert an anticancer drug, paclitaxel (PTX), to a class of prodrug hydrogelators with varying critical gelation concentrations.

Self-assembling prodrugs.

Covalent modification of therapeutic compounds is a clinically proven strategy to devise prodrugs with enhanced treatment efficacies. This prodrug strategy relies on the modified drugs that possess advantageous pharmacokinetic properties and administration routes over their parent drug. Self-assembling prodrugs represent an emerging class of therapeutic agents capable of spontaneously associating into well-defined supramolecular nanostructures in aqueous solutions.

Nanotherapeutic systems for local treatment of brain tumors.

Malignant brain tumor, including the most common type glioblastoma, are histologically heterogeneous and invasive tumors known as the most devastating neoplasms with high morbidity and mortality. Despite multimodal treatment including surgery, radiotherapy, chemotherapy, and immunotherapy, the disease inevitably recurs and is fatal. This lack of curative options has motivated researchers to explore new treatment strategies and to develop new drug delivery systems (DDSs); however, the unique anatomical, physiological, and pathological features of brain tumors greatly limit the effectiveness of conventional chemotherapy.