dioleoylphosphatidic-acid and Neoplasms

Radiodynamic therapy (RDT), an emerging therapeutic approach for cancer treatment by employing ionizing irradiation to induce localized photodynamic therapy (PDT) can overcome the drawbacks of the limited penetration depth for traditional PDT and the unconcentrated energy in the tumor for traditional radiotherapy (RT). Taking advantage of aggregation-induced emission (AIE) photosensitizers with bright fluorescence and efficient singlet oxygen production in the aggregate state, Hf-AIE coordination polymer nanoparticles (CPNs), which show both strong RT and RDT effect under X-ray irradiation, are developed. Furthermore, to enhance the tumor accumulation and prolong the tumor retention of the CPNs, bioorthogonal click chemistry is applied in the system through coupling between dibenzocyclooctyne (DBCO)-modified CPNs (Hf-AIE-PEG-DBCO) (PEG: poly(ethylene glycol)) and azide groups on the cell membrane formed by metabolic glycoengineering. Thanks to the high penetration of X-ray irradiation, the bioorthogonal-assisted RT and RDT combination therapy realizes significant killing of cancer cells without showing noticeable biotoxicity after intravenous administration of CPNs.

Topics: Animals; Antineoplastic Agents; Biological Transport; Cell Line, Tumor; Cell Membrane Permeability; Cell Proliferation; Cyclooctanes; Hafnium; Humans; Mice; Nanoparticles; Neoplasms; Neoplasms, Experimental; Phosphatidic Acids; Photochemotherapy; Photosensitizing Agents; Polyethylene Glycols; Singlet Oxygen

High stability and extended circulation time in vivo are quite favorable for practical biomedical applications of nanomaterials, because they greatly facilitate the preferential tumor accumulation of nanomaterials, resulting in enhanced signal fidelity for imaging and improved therapeutic effect for treatment. Although many surface modification approaches have been employed to improve the stability and circulating behavior of nanomaterials, it still remains challenging in acquiring stable and long-lasting nanomaterials for in vivo bioimaging and therapy, especially for nanoscale metal-organic frameworks (NMOFs) due to their intrinsic instability in physiological conditions. Herein, a facile, one-step strategy is reported to encapsulate the zirconium (Zr)-based NMOF UiO-66 within 1,2-dioleoyl-sn-glycero-3-phosphate (DOPA) lipid bilayer (DOPA-LB). Contrary to UiO-66 NMOFs functionalized with polyethylene glycol, the obtained UiO-66@DOPA-LB presents significantly enhanced stability and impressive blood circulation time, allowing a higher accumulation of UiO-66@DOPA-LB in the tumor tissue. Benefited from these meritorious features, UiO-66@DOPA-LB labeled with near-infrared dye, IRDye 800CW, can not only achieve highly sensitive imaging of breast cancer tumor (5 mm), but also exhibits superior capability for early tumor (1-2 mm) detection. This study enriches the surface modification approach of NMOFs, and is of great importance for practical application of NMOFs in biomedical areas.

Topics: Animals; Breast Neoplasms; Cell Line, Tumor; Female; Lipid Bilayers; Materials Testing; Metal-Organic Frameworks; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Nanostructures; Neoplasm Transplantation; Neoplasms; Phosphatidic Acids; Polyethylene Glycols; Surface Properties; Zirconium

Calcium phosphate (CaP) nanoparticles (NP) with an asymmetric lipid bilayer coating have been designed for targeted delivery of siRNA to the tumor. An anionic lipid, dioleoylphosphatydic acid (DOPA), was employed as the inner leaflet lipid to coat the nano-size CaP cores, which entrap the siRNA, such that the coated cores were soluble in organic solvent. A suitable neutral or cationic lipid was used as the outer leaflet lipid to form an asymmetric lipid bilayer structure verified by the measurement of NP zeta potential. The resulting NP was named LCP-II with a size of about 25 to 30nm in diameter and contained a hollow core as revealed by TEM imaging. PEGylation of NP was done by including a PEG-phospholipid conjugate, with or without a targeting ligand anisamide, in the outer leaflet lipid mixture. The sub-cellular distribution studied in the sigma receptor positive human H460 lung cancer cells indicated that LCP-II could release more cargo to the cytoplasm than our previous lipid/protamine/DNA (LPD) formulation, leading to a significant (~40 fold in vitro and ~4 fold in vivo) improvement in siRNA delivery. Bio-distribution study showed that LCP-II required more PEGylation for MPS evasion than the previous LPD, probably due to increased surface curvature in LCP-II.

Topics: Animals; Calcium Phosphates; Cell Line, Tumor; Fatty Acids, Monounsaturated; Female; Gene Silencing; Gene Transfer Techniques; Humans; Lipid Bilayers; Mice; Mice, Nude; Nanoparticles; Neoplasms; Phosphatidic Acids; Phosphatidylcholines; Quaternary Ammonium Compounds; RNA, Small Interfering