-
Polymers Feb 2024Liposomes show promise for anti-cancer drug delivery and tumor-targeted therapy. However, complex tumor microenvironments and the performance limitations of traditional...
Liposomes show promise for anti-cancer drug delivery and tumor-targeted therapy. However, complex tumor microenvironments and the performance limitations of traditional liposomes restrict clinical translation. Hyaluronic acid (HA)-modified nanoliposomes effectively target CD44-overexpressing tumor cells. Combination therapy enhances treatment efficacy and delays drug resistance. Here, we developed paclitaxel (PTX) liposomes co-modified with ginsenoside compound K (CK) and HA using film dispersion. Compared to cholesterol (Ch), CK substantially improved encapsulation efficiency and stability. In vitro release studies revealed pH-responsive behavior, with slower release at pH 7.4 versus faster release at pH 5. In vitro cytotoxicity assays demonstrated that replacing Ch with CK in modified liposomes considerably decreased HCT-116 cell viability. Furthermore, flow cytometry and fluorescence microscopy showed a higher cellular uptake of PTX-CK-Lip-HA in CD44-high cells, reflected in the lower half maximal inhibitory concentrations. Overall, CK/HA-modified liposomes represent an innovative, targeted delivery system for enhanced tumor therapy via pH-triggered drug release and CD44 binding.
PubMed: 38337294
DOI: 10.3390/polym16030405 -
Nature Communications Feb 2024The dynamic protein corona formed on nanocarriers has been revealed to strongly affect their in vivo behaviors. Precisely manipulating the formation of protein corona on...
The dynamic protein corona formed on nanocarriers has been revealed to strongly affect their in vivo behaviors. Precisely manipulating the formation of protein corona on nanocarriers may provide an alternative impetus for specific drug delivery. Herein, we explore the role of glycosylated polyhydroxy polymer-modified nanovesicles (CP-LVs) with different amino/hydroxyl ratios in protein corona formation and evolution. CP-LVs with an amino/hydroxyl ratio of approximately 0.4 (CP-LVs) are found to efficiently suppress immunoglobulin adsorption in blood and livers, resulting in prolonged circulation. Moreover, CP-LVs adsorb abundant tumor distinctive proteins, such as CD44 and osteopontin in tumor interstitial fluids, mediating selective tumor cell internalization. The proteins corona transformation specific to the environment appears to be affected by the electrostatic interaction between CP-LVs and proteins with diverse isoelectric points. Benefiting from surface modification-mediated protein corona regulation, paclitaxel-loaded CP-LVs demonstrate superior antitumor efficacy to PEGylated liposomes. Our work offers a perspective on rational surface-design of nanocarriers to modulate the protein corona formation for efficient drug delivery.
Topics: Polymers; Protein Corona; Nanoparticles; Drug Delivery Systems; Osteopontin
PubMed: 38326312
DOI: 10.1038/s41467-024-45254-7 -
Biomaterials Apr 2024Local anesthetics are effective in relieving pain, but their duration of action is short. Therefore, the development of injectable sustained release systems to prolong...
Local anesthetics are effective in relieving pain, but their duration of action is short. Therefore, the development of injectable sustained release systems to prolong the effect of local anesthetics has been of interest. In such systems delivering conventional local anesthetics, it has been challenging to achieve long durations of effect, particularly without incurring tissue toxicity. To overcome these challenges, we created a platform comprising a protein hydrogel incorporating hydrophobic local anesthetic (bupivacaine) nanoparticles. The nanoparticles were prepared by anti-solvent precipitation stabilized with bovine serum albumin (BSA), followed by crosslinking with glutaraldehyde (GA). The resulting BSA hydrogels prolonged release of bupivacaine in vitro. When bupivacaine nanoparticles within crosslinked BSA were injected at the sciatic nerve in rats, a duration of nerve block of 39.9 h was obtained, compared to 5.5 h for the commercial bupivacaine liposome suspension EXPAREL®. Tissue reaction was benign. We further demonstrated that this system could control the release of the amphiphilic drug diphenhydramine and the hydrophobic paclitaxel.
Topics: Rats; Animals; Anesthetics, Local; Anesthesia, Local; Hydrogels; Bupivacaine; Nerve Block
PubMed: 38316090
DOI: 10.1016/j.biomaterials.2024.122494 -
Journal of Clinical Oncology : Official... May 2024Literature evidence suggests that trabectedin monotherapy is effective in patients with recurrent ovarian cancer (OC) presenting mutation and/or BRCAness phenotype. (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Single-Agent Trabectedin Versus Physician's Choice Chemotherapy in Patients With Recurrent Ovarian Cancer With -Mutated and/or BRCAness Phenotype: A Randomized Phase III Trial.
PURPOSE
Literature evidence suggests that trabectedin monotherapy is effective in patients with recurrent ovarian cancer (OC) presenting mutation and/or BRCAness phenotype.
METHODS
A prospective, open-label, randomized phase III MITO-23 trial evaluated the activity and safety of trabectedin 1.3 mg/m given once every 3 weeks (arm A) in mutation carriers or patients with BRCAness phenotype (ie, patients who responded to ≥two previous platinum-based treatments) with recurrent OC, primary peritoneal carcinoma, or fallopian tube cancer in comparison with physician's choice chemotherapy in the control arm (arm B; pegylated liposomal doxorubicin, topotecan, gemcitabine, once-weekly paclitaxel, or carboplatin). The primary end point was overall survival (OS) evaluated in the intention-to-treat population.
RESULTS
Overall, 244 patients from 21 MITO centers were randomly assigned (arm A = 122/arm B = 122). More than 70% of patients received ≥three previous chemotherapy lines and 35.7% had received a poly (ADP-ribose) polymerase inhibitor (PARPi) before enrollment. Median OS was not significantly different between the arms: arm A: 15.8 versus arm B: 17.9 months ( = .304). Median progression-free survival was 4.9 months in arm A versus 4.4 months in arm B ( = .897). Among 208 patients evaluable for efficacy, the objective response rate was 17.1% in arm A and 21.4% in arm B, with comparable median duration of response (5.62 5.66 months, respectively). No superior effect was observed for trabectedin in the prespecified subgroup analyses according to mutational status, chemotherapy type, and pretreatment with a PARPi and/or platinum-free interval. Trabectedin showed a higher frequency of grade ≥3 adverse events (AEs), serious AEs, and serious adverse drug reactions compared with control chemotherapy.
CONCLUSION
Trabectedin did not improve median OS and showed a worse safety profile in comparison with physician's choice control chemotherapy.
Topics: Humans; Female; Trabectedin; Middle Aged; Ovarian Neoplasms; Aged; Adult; Mutation; Neoplasm Recurrence, Local; Phenotype; Prospective Studies; BRCA2 Protein; BRCA1 Protein; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Aged, 80 and over; Progression-Free Survival
PubMed: 38315944
DOI: 10.1200/JCO.23.01225 -
Journal of Controlled Release :... Mar 2024Chemotherapeutic efficacy for pancreatic cancer is severely compromised by limited drug availability to tumor cells. Herein, we constructed a cancer cell membrane-fused...
Chemotherapeutic efficacy for pancreatic cancer is severely compromised by limited drug availability to tumor cells. Herein, we constructed a cancer cell membrane-fused liposome containing a siATG5-loaded calcium phosphate (CaP) core, termed CLip@siATG5. Through cancer cell membrane camouflage, the liposomes evaded immune clearance, actively infiltrated tumor tissues, and were preferentially taken up by homotypic tumor cells. Then, siATG5 escaped from the endosomes and was liberated in the cytoplasm, mainly benefiting from CaP dissolution-induced endosome rupture and liposome disassembly in acidic endosomes. The released siATG5 silenced autophagy protein 5 (ATG5) to inhibit autophagy, starving tumor cells. An alternative nutrient procurement pathway, macropinocytosis, was then upregulated in the cells, leading to increased uptake of the albumin-bound chemotherapeutic agent (nanoparticle albumin-bound paclitaxel (Nab-PTX)). Finally, in a murine pancreatic cancer model, CLip@siATG5 combined with Nab-PTX exerted superior efficacy to a twofold dose of Nab-PTX while avoiding its toxicity. Overall, we justified enhancing chemotherapeutic delivery by modulating the pancreatic cancer cell metabolism, which will enlighten the development of more effective chemotherapeutic adjuvants for pancreatic cancer in the future.
Topics: Humans; Animals; Mice; Liposomes; Paclitaxel; Pancreatic Neoplasms; Albumins; Pancreas; Cell Membrane; Cell Line, Tumor; Nanoparticles; Albumin-Bound Paclitaxel
PubMed: 38311244
DOI: 10.1016/j.jconrel.2024.01.055 -
Frontiers in Oncology 2024Inflammatory breast cancer (IBC) is an aggressive and rare form of breast cancer with a poor prognosis. The occurrence of bilateral IBC in a short period of time is...
Inflammatory breast cancer (IBC) is an aggressive and rare form of breast cancer with a poor prognosis. The occurrence of bilateral IBC in a short period of time is extremely rare. In this case report, a 54-year-old woman diagnosed with invasive ductal carcinoma of the left breast underwent lumpectomy, lymph node dissection, chemotherapy, and radiotherapy but opted against trastuzumab treatment. Four years later, she experienced bilateral breast inflammation, skin changes, edema, and heat (calor). Biopsies confirmed breast cancer metastasis to both breasts. Whole-Exome Sequencing revealed genetic mutations, including PIK3CA and C4orf54, in both primary and recurrent tumors, with significant downregulation in the recurrent tumors. KEGG analysis suggested potential enrichment of axon guidance signal pathways in both tumors. The patient showed a partial response after treatment with liposome paclitaxel, along with targeted therapy using trastuzumab and pertuzumab. This case report sheds light on the rare occurrence of bilateral inflammatory breast cancer post-HER-2 treatment and highlights the importance of genetic profiling in understanding the disease. Further research on clinical targets for breast cancer management is warranted.
PubMed: 38283858
DOI: 10.3389/fonc.2024.1276637 -
Gynecologic Oncology May 2024The addition of bevacizumab to chemotherapy for platinum-resistant (PL-R) ovarian cancer (OC) improved progression-free (PFS) but not overall survival (OS) in clinical...
OBJECTIVES
The addition of bevacizumab to chemotherapy for platinum-resistant (PL-R) ovarian cancer (OC) improved progression-free (PFS) but not overall survival (OS) in clinical trials. We explored real-world outcomes in Ontario, Canada, and compared survival in the pre- and post-bevacizumab era.
METHODS
Administrative databases were utilized to identify all patients treated with bevacizumab for PL-R OC. Time on treatment (ToT) was used as surrogate for PFS. Median OS was determined using the Kaplan-Meier method. Factors associated with ToT/OS were identified using a Cox proportional hazard model. A before and after comparative effectiveness analysis was performed to determine mOS for patients treated pre- and post-bevacizumab approval.
RESULTS
From 2017 to 2019, 176 patients received bevacizumab. Median ToT was 3 months and OS was 11 months. Sixty-four percent received liposomal doxorubicin and 34% received paclitaxel. ToT (6 vs 3 months; HR 0.44; p < 0.0001) and OS (14 vs 9 months; HR 0.45; p = 0.0089) were longer with bevacizumab/paclitaxel. OS was not significantly different pre- and post-bevacizumab funding (8 vs 9 months; HR 1.01; 0.937). Median OS increased for those receiving paclitaxel (6 vs 11 months), but those in the post group were younger, more likely to have undergone primary surgery and had less co-morbidities.
CONCLUSION
Real-world outcomes with bevacizumab in PL-R OC are inferior to those in the pivotal clinical trial. Survival has not significantly improved since funding became publicly available, indicating a substantial efficacy-effectiveness gap between trial and real-world outcomes. Median OS and ToT were significantly better when bevacizumab was given with paclitaxel.
Topics: Humans; Bevacizumab; Female; Antineoplastic Combined Chemotherapy Protocols; Ovarian Neoplasms; Middle Aged; Aged; Drug Resistance, Neoplasm; Paclitaxel; Progression-Free Survival; Ontario; Adult; Doxorubicin; Retrospective Studies; Carcinoma, Ovarian Epithelial; Aged, 80 and over; Polyethylene Glycols
PubMed: 38281412
DOI: 10.1016/j.ygyno.2024.01.027 -
Acta Pharmaceutica Sinica. B Jan 2024Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer, although it is limited by the low tumor delivery efficacy of anticancer drugs....
Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer, although it is limited by the low tumor delivery efficacy of anticancer drugs. Bacterial therapy is emerging for cancer treatment due to its high immune stimulation effect; however, excessively generated immunogenicity will cause serious inflammatory response syndrome. Here, we prepared cancer cell membrane-coated liposomal paclitaxel-loaded bacterial ghosts (LP@BG@CCM) by layer-by-layer encapsulation for the treatment of metastatic lung cancer. The preparation processes were simple, only involving film formation, electroporation, and pore extrusion. LP@BG@CCM owned much higher 4T1 cancer cell toxicity than LP@BG due to its faster fusion with cancer cells. In the 4T1 breast cancer metastatic lung cancer mouse models, the remarkably higher lung targeting of intravenously injected LP@BG@CCM was observed with the almost normalized lung appearance, the reduced lung weight, the clear lung tissue structure, and the enhanced cancer cell apoptosis compared to its precursors. Moreover, several major immune factors were improved after administration of LP@BG@CCM, including the CD4/CD8a T cells in the spleen and the TNF-, IFN-, and IL-4 in the lung. LP@BG@CCM exhibits the optimal synergistic chemo-immunotherapy, which is a promising medication for the treatment of metastatic lung cancer.
PubMed: 38261850
DOI: 10.1016/j.apsb.2023.08.012 -
Pharmaceutics Jan 2024Breast cancer (BC) has become the fifth most prevalent cause of cancer-related morbidity, attracting significant attention from researchers due to its heightened... (Review)
Review
Breast cancer (BC) has become the fifth most prevalent cause of cancer-related morbidity, attracting significant attention from researchers due to its heightened malignancy and drug resistance. Conventional chemotherapy approaches have proven inadequate in addressing all BC subtypes, highlighting the urgent need for novel therapeutic approaches or drugs. Curcumin (CUR), a phytochemical derived from Curcuma longa (turmeric), has shown substantial potential in inhibiting BC cell migration, metastasis, and proliferation. However, the use of CUR in this context comes with challenges due to its dynamic and easily degradable nature, poor aqueous solubility, low bioavailability, rapid metabolism, and swift systemic elimination, collectively limiting its clinical applications. As such, we provide an overview of the properties, synthesis, and characterization of the hybridization of CUR and its analogue with chemo-drug building blocks. We reviewed research from the last five years on CUR's biogenesis with respect to the regulation of BC, revealing that CUR participates in arresting BC cells in the cell cycle and significantly induces apoptosis in BC cells. Information on the chemotherapeutic and antitumor mechanisms of CUR in BC, including regulation of the cell cycle, increased cell apoptosis, and inhibition of multidrug resistance (MDR), was compiled. Additionally, we provide an overview of CUR loaded into nanomaterials that are cotreated with other chemotherapeutic drugs, such as paclitaxel, thymoquinone, and tamoxifen. In this review, we discuss different types of nanoparticles that can be used for CUR delivery, such as polymeric nanoparticles, carbon nanotubes, and liposomes. By comparing the size, entrapment efficiency, drug-loading capacity, release time, biocompatibility, pharmaceutical scale, and reproducibility of various nanomaterials, we aimed to determine which formulations are better suited for loading CUR or its analogue. Ultimately, this review is expected to offer inspiring ideas, promising strategies, and potential pathways for developing advanced anti-BC strategy nanosystems in clinical practice.
PubMed: 38258090
DOI: 10.3390/pharmaceutics16010079 -
BMC Cancer Jan 2024Paclitaxel liposome (Lipusu) is known to be effective in non-small cell lung cancer (NSCLC) as first-line treatment. This study aimed to evaluate the effectiveness and...
BACKGROUND
Paclitaxel liposome (Lipusu) is known to be effective in non-small cell lung cancer (NSCLC) as first-line treatment. This study aimed to evaluate the effectiveness and safety of paclitaxel liposome based chemotherapy plus PD-1/PD-L1 inhibitor in patients with advanced NSCLC.
METHODS
In this multicenter, retrospective, real-world study, patients with advanced NSCLC who were administered paclitaxel liposome based chemotherapy plus PD-1/PD-L1 inhibitor in three centers (Peking University People's Hospital as the lead center) in China between 2016 and 2022 were included. Progression-free survival (PFS), overall survival (OS), objective response rate, disease control rate, and adverse events (AEs) were evaluated.
RESULTS
A total of 49 patients were included, with 33 (67.3%) receiving paclitaxel liposome based chemotherapy plus PD-1/PD-L1 inhibitor as first-line treatment. There were 34 patients (69.4%) diagnosed with squamous cell carcinoma and 15 (30.6%) with adenocarcinoma. The median follow-up was 20.5 (range: 3.1-41.1) months. The median PFS and OS of all patients were 9.7 months (95% confidence interval [CI], 7.0-12.4) and 30.5 months (95% CI, not evaluable-not evaluable), respectively. Patients with squamous cell carcinoma and adenocarcinoma had median PFS of 11 months (95%CI, 6.5-15.5) and 9.3 months (95%CI, 7.0-12.4), respectively. The median PFS was 9.9 months (95%CI, 7.1-12.7) in patients who received the combined regimen as first-line treatment. Treatment-related AEs of any grade were observed in 25 (51.0%) patients, and AEs of grade 3 or worse were observed in nine patients (18.4%). The most common treatment-related AEs were myelosuppression (14.3%) and fever (10.2%).
CONCLUSIONS
Paclitaxel liposome based chemotherapy plus PD-1/PD-L1 inhibitor prolonged the PFS in advanced NSCLC with acceptable safety, which was worthy of clinical application.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Paclitaxel; Lung Neoplasms; Liposomes; Immune Checkpoint Inhibitors; Programmed Cell Death 1 Receptor; Retrospective Studies; Immunotherapy; Antineoplastic Combined Chemotherapy Protocols; Adenocarcinoma; Carcinoma, Squamous Cell
PubMed: 38238648
DOI: 10.1186/s12885-024-11860-3