Nuclear-targeted therapy has received increasing attention as a potential strategy to improve the therapeutic efficacy of treating cancer. The main challenges include targeting, drug-delivery efficiency and release of anticancer agents to the cancer cell nucleus. Nanoparticles as nanocarriers have started to address some of these issues. However, a lack of understanding in how nanoconstructs interact with the nucleus has precluded detailed studies. In this article, we highlight a nanoconstruct composed of gold (Au) nanostars loaded with nucleolin-specific aptamers. This nanoconstruct induced major changes in the nuclear phenotype through nuclear envelope (NE) invaginations. Femtosecond, light-triggered release of the aptamers from the surface of the Au nanostars further increased the number of NE deformations. Cancer cells with more NE folding showed increased apoptosis as well as decreased cell viability. The author's of this article have revealed that correlation between drug-induced changes in nuclear phenotypes and increased therapeutic efficacy can provide new insight into nuclear-targeted cancer therapy.
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http://dx.doi.org/10.4155/tde.12.107 | DOI Listing |
Nanoscale
January 2025
Soft Matter Nanotechnology, Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), Paseo de Miramon 194, 20014, Donostia-San Sebastián, Spain.
Targeted delivery offers solutions for more efficient therapies with fewer side effects. Here, lipopeptides (LPs) prepared by conjugation of the nuclear-targeting peptide analogue H-YKQSHKKGGKKGSG-NH (NrTP6) and two lauric acid chains are used to encapsulate the chemotherapeutic agent doxorubicin (DX) through a solvent-exchange protocol. LPs spontaneously form nanosized rod-like assemblies in phosphate buffer.
View Article and Find Full Text PDFJ Colloid Interface Sci
February 2025
Henan Key Laboratory of Natural Medicine Innovation and Transformation, Henan University, Kaifeng 475004, China; State Key Laboratory of Antiviral Drugs, Henan University, Kaifeng 475004, China; The Zhongzhou Laboratory for Integrative Biology, Henan University, Kaifeng, China. Electronic address:
Smart nanoplatforms designed for nuclear-targeted delivery of chemotherapeutic agents to tumor sites are pivotal in advancing tumor treatment and immunotherapy. Herein, we introduced a novel nuclear-targeting double-shell smart nanoplatform (HMCuS/Pt/ICG@MnO@9R-P201 (HMCPIM9P)), which synergistically enhances chemotherapy, photodynamic therapy (PDT), photothermal therapy (PTT), immunotherapy and chemodynamic therapy (CDT). The core of this nanoplatform consists of double-shell multifunctional nanoparticles (HMCuS@MnO) that enable targeted delivery of the photosensitizer Indocyanine Green (ICG) and the chemotherapeutic agent cisplatin (Pt).
View Article and Find Full Text PDFBiomaterials
February 2025
Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, School of Pharmacy, Fujian Medical University, Fuzhou, 350004, China. Electronic address:
Gene therapy offers a promising avenue for treating ischemic diseases, yet its clinical efficacy is hindered by the limitations of single gene therapy and the high oxidative stress microenvironment characteristic of such conditions. Lipid-polymer hybrid vectors represent a novel approach to enhance the effectiveness of gene therapy by harnessing the combined advantages of lipids and polymers. In this study, we engineered lipid-polymer hybrid nanocarriers with tailored structural modifications to create a versatile membrane fusion lipid-nuclear targeted polymer nanodelivery system (FLNPs) optimized for gene delivery.
View Article and Find Full Text PDFAdv Drug Deliv Rev
August 2024
Department of Chemistry, University of Basel, BPR 1096, Mattenstrasse 22, 4058 Basel, Switzerland; NCCR-Molecular Systems Engineering, BPR 1095, Mattenstrasse 24a, 4058 Basel, Switzerland. Electronic address:
One of the key aspects of coping efficiently with complex pathological conditions is delivering the desired therapeutic compounds with precision in both space and time. Therefore, the focus on nuclear-targeted delivery systems has emerged as a promising strategy with high potential, particularly in gene therapy and cancer treatment. Here, we explore the design of supramolecular nanoassemblies as vehicles to deliver specific compounds to the nucleus, with the special focus on polymer and peptide-based carriers that expose nuclear localization signals.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
May 2024
Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610.
Successful CRISPR/Cas9-based gene editing in skeletal muscle is dependent on efficient propagation of Cas9 to all myonuclei in the myofiber. However, nuclear-targeted gene therapy cargos are strongly restricted to their myonuclear domain of origin. By screening nuclear localization signals and nuclear export signals, we identify "Myospreader," a combination of short peptide sequences that promotes myonuclear propagation.
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