<p>Ovarian cancer remains the most lethal gynaecologic malignancy, primarily because it is often diagnosed at a late stage, exhibits extensive intraperitoneal dissemination and frequently acquires resistance to chemotherapy. Recombinant therapeutic cargos, including engineered proteins, peptides, nucleic acids, antibody fragments and ligand-drug fusion constructs have emerged as powerful molecularly targeted agents. These biologics can modulate oncogenic signaling pathways, reprogram the immune microenvironment and reverse drug resistance. However, their clinical utility is constrained by rapid clearance from the circulation, susceptibility to enzymatic degradation and poor penetration into solid tumors. Nano-delivery systems provide a transformative platform to overcome these limitations by improving systemic stability, extending half-life, enhancing bioavailability and increasing tumor selectivity. Through mechanisms, such as receptor-mediated endocytosis and enhanced permeation and retention (EPR) effect, nanocarriers facilitate efficient tumor targeting and intracellular trafficking of recombinant cargos. Once internalized, these agents can engage and disrupt critical oncogenic pathways for example, suppressing phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/ mechanistic target of rapamycin (mTOR) signaling, inhibiting Wnt/β-catenin activation or perturbing deoxyribonucleic acid (DNA) damage repair networks thereby inducing apoptosis or sensitizing cancer cells to subsequent therapy. Despite compelling preclinical data, clinical translation remains challenging issues, such as patient stratification, identification of predictive biomarkers and optimization of controlled release kinetics must be addressed. Future directions include programmable nanocarriers, ligand-gated release systems and combination nano-therapies that simultaneously deliver multiple cargos to maximize anti-tumor efficacy.</p> Graphical Abstract <p></p>

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Targeted Nano-delivery of Recombinant Therapeutic Cargos for Ovarian Cancer: Advances in Molecular Pharmacodynamics and Pharmacokinetics

  • Om Chandrakar,
  • Trilochan Satapathy,
  • Poonam Sahu,
  • Kamlesh Sahu

摘要

Ovarian cancer remains the most lethal gynaecologic malignancy, primarily because it is often diagnosed at a late stage, exhibits extensive intraperitoneal dissemination and frequently acquires resistance to chemotherapy. Recombinant therapeutic cargos, including engineered proteins, peptides, nucleic acids, antibody fragments and ligand-drug fusion constructs have emerged as powerful molecularly targeted agents. These biologics can modulate oncogenic signaling pathways, reprogram the immune microenvironment and reverse drug resistance. However, their clinical utility is constrained by rapid clearance from the circulation, susceptibility to enzymatic degradation and poor penetration into solid tumors. Nano-delivery systems provide a transformative platform to overcome these limitations by improving systemic stability, extending half-life, enhancing bioavailability and increasing tumor selectivity. Through mechanisms, such as receptor-mediated endocytosis and enhanced permeation and retention (EPR) effect, nanocarriers facilitate efficient tumor targeting and intracellular trafficking of recombinant cargos. Once internalized, these agents can engage and disrupt critical oncogenic pathways for example, suppressing phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/ mechanistic target of rapamycin (mTOR) signaling, inhibiting Wnt/β-catenin activation or perturbing deoxyribonucleic acid (DNA) damage repair networks thereby inducing apoptosis or sensitizing cancer cells to subsequent therapy. Despite compelling preclinical data, clinical translation remains challenging issues, such as patient stratification, identification of predictive biomarkers and optimization of controlled release kinetics must be addressed. Future directions include programmable nanocarriers, ligand-gated release systems and combination nano-therapies that simultaneously deliver multiple cargos to maximize anti-tumor efficacy.

Graphical Abstract