Nanoscale Liposomes Co-Loaded with Irinotecan Hydrochloride and Thalidomide for Colorectal Cancer Synergistic Therapy.

Irinotecan hydrochloride (CPT-11) is one of the first-line drugs used in the clinical treatment of colorectal cancer (CRC). However, the concomitant adverse effect of delayed diarrhea has hindered its clinical use. CPT-11 combined with Thalidomide (THA) therapy is considered a palliative strategy.

Near Infrared-Activatable Biomimetic Nanoplatform for Tumor-Specific Drug Release, Penetration and Chemo-Photothermal Synergistic Therapy of Orthotopic Glioblastoma.

Introduction: Glioblastoma multiforme (GBM), a highly invasive and prognostically challenging brain cancer, poses a significant hurdle for current treatments due to the existence of the blood-brain barrier (BBB) and the difficulty to maintain an effective drug accumulation in deep GBM lesions.

Methods: We present a biomimetic nanoplatform with angiopep-2-modified macrophage membrane, loaded with indocyanine green (ICG) templated self-assembly of SN38 (AM-NP), facilitating active tumor targeting and effective blood-brain barrier penetration through specific ligand-receptor interaction.

Results: Upon accumulation at tumor sites, these nanoparticles achieved high drug concentrations.

Biological impact and therapeutic potential of a novel camptothecin derivative (FLQY2) in pancreatic cancer through inactivation of the PDK1/AKT/mTOR pathway.

Background: Camptothecin (CPT), a pentacyclic alkaloid with antitumor properties, is derived from the Camptotheca acuminata. Topotecan and irinotecan (CPT derivatives) were first approved by the Food and Drug Administration for cancer treatment over 25 years ago and remain key anticancer drugs today. However, their use is often limited by clinical toxicity.

Design, synthesis, and bioactivity evaluation of novel indole-selenide derivatives as P-glycoprotein inhibitors against multi-drug resistance in MCF-7/ADR cell.

The inhibition of P-glycoprotein (P-gp) has emerged as an intriguing strategy for circumventing multidrug resistance (MDR) in anticancer chemotherapy. In this study, we have designed and synthesized 30 indole-selenides as a new class of P-gp inhibitors based on the scaffold hopping strategy. Among them, the preferred compound H27 showed slightly stronger reversal activity (reversal fold: 271.

Protein and peptide-based renal targeted drug delivery systems.

Renal diseases have become an increasingly concerned public health problem in the world. Kidney-targeted drug delivery has profound transformative potential on increasing renal efficacy and reducing extra-renal toxicity. Protein and peptide-based kidney targeted drug delivery systems have garnered more and more attention due to its controllable synthesis, high biocompatibility and low immunogenicity.

KPNB1-mediated nuclear import in cancer.

Dysregulation of nucleocytoplasmic shuttling impairs cellular homeostasis and promotes cancer development. KPNB1 is a member of karyopherin β family, mediating the transportation of proteins from the cytoplasm to the nucleus. In a variety of cancers, the expression of KPNB1 is upregulated to facilitate tumor growth and progression.

Inhaled nano-based therapeutics for pulmonary fibrosis: recent advances and future prospects.

It is reported that pulmonary fibrosis has become one of the major long-term complications of COVID-19, even in asymptomatic individuals. Currently, despite the best efforts of the global medical community, there are no treatments for COVID-induced pulmonary fibrosis. Recently, inhalable nanocarriers have received more attention due to their ability to improve the solubility of insoluble drugs, penetrate biological barriers of the lungs and target fibrotic tissues in the lungs.

Enhanced Transdermal Peptide-Modified Flexible Liposomes for Efficient Percutaneous Delivery of Chrysomycin A to Treat Subcutaneous Melanoma and Intradermal MRSA Infection.

Superficial skin diseases, including skin infections and tumors, are common healthcare burdens. In this study, the in vivo activity of chrysomycin A (CA) is explored, and a transdermal liposomal CA formulation is further constructed for the simultaneous treatment of cutaneous melanoma and cutaneous methicillin-resistant Staphylococcus aureus (MRSA) infection. The prepared liposomes (TD-LP-CA) display a strong antitumor effect with an IC value of less than 0.

Discovery of 2,5-disubstituted furan derivatives featuring a benzamide motif for overcoming P-glycoprotein mediated multidrug resistance in MCF-7/ADR cell.

P-glycoprotein (P-gp) is one of the drug efflux transporters that triggers multidrug resistance (MDR) in cells. Herein, by utilizing the strategies of active skeleton splicing and structural optimization on the lead compound 5 m, a total of 50 novel 2,5-disubstituted furan derivatives were designed, synthesized, and screened for P-gp inhibitory activity. The structure-activity relationship analysis enabled the identification of an important pharmacophore N-phenylbenzamide, which resulted in the discovery of a promising drug lead compound Ⅲ-8.

Supramolecular Filament Hydrogel as a Universal Immunomodulator Carrier for Immunotherapy Combinations.

A major challenge of cancer immunotherapy is to develop delivery strategies that can effectively and safely augment the immune system's antitumor response. Here, we report on the design and synthesis of a peptide-based supramolecular filament (SF) hydrogel as a universal carrier for localized delivery of three immunomodulating agents of distinct action mechanisms and different molecular weights, including an aPD1 antibody, an IL15 cytokine, and a STING agonist (CDA). We show that hydrogelation can be triggered to occur upon intratumoral injection of SF solutions containing each of aPD1, IL15, or CDA.

Novel Benzo Five-Membered Heterocycle Derivatives as P-Glycoprotein Inhibitors: Design, Synthesis, Molecular Docking, and Anti-Multidrug Resistance Activity.

A proposed strategy to overcome multidrug resistance (MDR) of anticancer drugs in chemotherapy is to disable the efflux function of P-glycoprotein (P-gp). In this study, based on ring-merging and fragment-growing strategies, 105 novel benzo five-membered heterocycle derivatives were designed, synthesized, and screened. Exploration of the structure-activity relationship (SAR) led to the identification of with low cytotoxicity and promising reversal activity to doxorubicin in MCF-7/ADR cells.

Design, synthesis and biological evaluation of novel phenylfuran-bisamide derivatives as P-glycoprotein inhibitors against multidrug resistance in MCF-7/ADR cell.

The co-administration of anticancer drugs and P-glycoprotein (P-gp) inhibitors was a treatment strategy to surmount multidrug resistance (MDR) in anticancer chemotherapy. In this study, novel phenylfuran-bisamide derivatives were designed as P-gp inhibitors based on target-based drug design, and 31 novel compounds were synthesized and screened on MCF-7/ADR cells. The result of bioassay revealed that compound y12d exhibited low cytotoxicity and promising MDR reversal activity (IC = 0.

Preparation of a camptothecin analog FLQY2 self-micelle solid dispersion with improved solubility and bioavailability.

Background: 7-p-trifluoromethylphenyl-FL118 (FLQY2) is a camptothecin analog with excellent antitumor efficacy against various solid tumors. However, its poor solubility and low bioavailability limited the development of the drug. Polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus), an emerging carrier for preparing solid dispersion (SD), encapsulated FLQY2 to circumvent the above limitations.

Design, synthesis and biological evaluation of rhein-piperazine-dithiocarbamate hybrids as potential anticancer agents.

A series of novel rhein-piperazine-dithiocarbamate hybrids 3 were efficiently synthesized from rhein through a catalyst-free and one-pot, three-step sequence involving chlorination and N-acylation followed by dithiocarbamate formation. Hybrids 3 were evaluated for their in vitro cytotoxic potency by MTT assay against several human cancer and non-cancer cells. Five of the hybrids were more cytotoxic to human lung cancer cell line A549 than the parent rhein and the reference, cytarabine (CAR).

Formulation of Chrysomycin A Cream for the Treatment of Skin Infections.

Chrysomycin A, a compound derived from marine microorganisms, proved to have a specific great in vitro inhibitory effect on methicillin-resistant (MRSA). It exhibits high safety for the skin, as well as a better therapeutic effect than the current clinical drug, vancomycin. Nevertheless, its poor water solubility highly limits the application and reduces the bioavailability.

N-acylhomoserine lactonase-based hybrid nanoflowers: a novel and practical strategy to control plant bacterial diseases.

Background: The disease caused by plant pathogenic bacteria in the production, transportation, and storage of many crops has brought huge losses to agricultural production. N-acylhomoserine lactonases (AHLases) can quench quorum-sensing (QS) by hydrolyzing acylhomoserine lactones (AHLs), which makes them the promising candidates for controlling infections of QS-dependent pathogenic bacteria. Although many AHLases have been isolated and considered as a potentially effective preventive and therapeutic agents for bacterial diseases, the intrinsically poor ambient stability has seriously restricted its application.

Design, Synthesis, and Biological Evaluation of Artemisinin-Piperazine-Phosphoramide Mustard Hybrids as Potential Anticancer Agents.

A series of novel artemisinin-piperazine-phosphoramide mustard (PPM) hybrids were designed and synthesized by incorporating phosphoramide mustard (PM) into dihydroartemisinin (DHA) via an efficient, catalyst-free two-step sequential substitution. Artemisinin-PPM hybrids showed better cytotoxic potency against HepG2 cells than both the parent DHA and the reference, vincristine (VCR). Structure-activity relationship (SAR) studies showed that the cytotoxicity was significantly enhanced by the introduction of a thiazole moiety.

Investigation of the Uptake and Transport of Two Novel Camptothecin Derivatives in Caco-2 Cell Monolayers.

Irinotecan and Topotecan are two Camptothecin derivatives (CPTs) whose resistance is associated with the high expression of breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp). To reverse this resistance, two novel CPTs, FL77-28 (7-(3-Fluoro-4-methylphenyl)-10,11-methylenedioxy-20(S)-CPT) and FL77-29 (7-(4-Fluoro-3-methylphenyl)-10,11-methylenedioxy-20(S)-CPT), were synthesized by our group. In this study, the anti-tumor activities of FL77-28, FL77-29, and their parent, FL118 (10,11-methylenedioxy-20(S)-CPT), were evaluated and the results showed that FL77-28 and FL77-29 had stronger anti-tumor activities than FL118.

Legumain/pH dual-responsive lytic peptide-paclitaxel conjugate for synergistic cancer therapy.

After molecule targeted drug, monoclonal antibody and antibody-drug conjugates (ADCs), peptide-drug conjugates (PDCs) have become the next generation targeted anti-tumor drugs due to its properties of low molecule weight, efficient cell penetration, low immunogenicity, good pharmacokinetic and large-scale synthesis by solid phase synthesis. Herein, we present a lytic peptide PTP7-drug paclitaxel conjugate assembling nanoparticles (named PPP) that can sequentially respond to dual stimuli in the tumor microenvironment, which was designed for passive tumor-targeted delivery and on-demand release of a tumor lytic peptide (PTP-7) as well as a chemotherapeutic agent of paclitaxel (PTX). To achieve this, tumor lytic peptide PTP-7 was connected with polyethylene glycol by a peptide substrate of legumain to serve as hydrophobic segments of nanoparticles to protect the peptide from enzymatic degradation.

Mechanochemical preparation of triptolide-loaded self-micelle solid dispersion with enhanced oral bioavailability and improved activity.

Triptolide (TP), a compound isolated from a Chinese medicinal herb, possesses potent anti-tumor, immunosuppressive, and anti-inflammatory properties, but was clinically limited due to its poor solubility, bioavailability, and toxicity. Considering the environment-friendly, low-cost mechanochemical techniques and potential dissolution enhancement ability of NaGA, an amorphous solid dispersion (NaGA&TP-BM) consisting of TP and NaGA were well-prepared to address these issues. The performance of NaGA&TP-BM was improved through ball milling, such as from crystalline state to an amorphous solid dispersion, suitable nano micelle size and surface potential, and increased solubility.

Therapeutic supramolecular tubustecan hydrogel combined with checkpoint inhibitor elicits immunity to combat cancer.

The clinical benefit of PD-1/PD-L1 blockade immunotherapy is substantially restricted by insufficient infiltration of T lymphocytes into tumors and compromised therapeutic effects due to immune-related adverse events following systemic administration. Some chemotherapeutic agents have been reported to trigger tumor-associated T cell responses, providing a promising strategy to achieve potent immune activation in a synergistic manner with PD-1 blockade immunotherapy. In light of this, a localized chemoimmunotherapy system was developed using an anti-cancer drug-based supramolecular polymer (SP) hydrogel to "re-edit" the host's immune system to combat cancer.

Tonkinensine B induces apoptosis through mitochondrial dysfunction and inactivation of the PI3K/AKT pathway in triple-negative breast cancer cells.

Objectives: Tonkinensine B, a novel compound with cytisine-pterocarpan skeleton isolated from the root of Sophora tonkinensis Gagnep, was reported to have a significant antitumor effect. The effect and intrinsic mechanism of tonkinensine B on tumour need to be further investigated.

Methods: With the help of cell cytotoxicity, the effect of tonkinensine B on MDA-MB-231 cells was investigated.