ABSTRACT
Nanomaterial-based in vivo tumor imaging and therapy have attracted extensive attention; however, they suffer from the unintelligent "always ON" or single-parameter responsive signal output, substantial off-target effects, and high cost. Therefore, achieving in vivo easy-to-read tumor imaging and precise therapy in a multi-parameter responsive and intelligent manner remains challenging. Herein, an intelligent DNA nanoreactor (iDNR) was constructed following the "AND" Boolean logic algorithm to address these issues. iDNR-mediated in situ deposition of photothermal substance polydopamine (PDA) can only be satisfied in tumor tissues with abundant membrane protein biomarkers "AND" hydrogen peroxide (H2 O2 ). Therefore, intelligent temperature-based in vivo easy-to-read tumor imaging is realized without expensive instrumentation, and its diagnostic performance matches with that of flow cytometry, and photoacoustic imaging. Moreover, precise photothermal therapy (PTT) of tumors could be achieved via intelligent heating of tumor tissues. The precise PTT of primary tumors in combination with immune checkpoint blockade (ICB) therapy suppresses the growth of distant tumors and inhibits tumor recurrence. Therefore, highly programmable iDNR is a powerful tool for intelligent biomedical applications.
Subject(s)
Nanoparticles , Nanostructures , Neoplasms , Humans , Neoplasms/diagnostic imaging , Neoplasms/therapy , Neoplasms/pathology , Phototherapy/methods , Nanotechnology , Cell Line, Tumor , Tumor MicroenvironmentABSTRACT
Current clinical approaches to osteoporosis primarily target osteoclast biology, overlooking the synergistic role of bone cells, immune cells, cytokines, and inorganic components in creating an abnormal osteoporotic microenvironment. Here, metal-polyDNA nanoparticles (Ca-polyCpG MDNs) composed of Ca2+ and ultralong single-stranded CpG sequences were developed to reconstruct the osteoporotic microenvironment and suppress osteoporosis. Ca-polyCpG MDNs can neutralize osteoclast-secreted hydrogen ions, provide calcium repletion, promote remineralization, and repair bone defects. Besides, the immune-adjuvant polyCpG in MDNs could induce the secretion of osteoclastogenesis inhibitor interleukin-12 and reduce the expression of osteoclast function effector protein to inhibit osteoclast differentiation, further reducing osteoclast-mediated bone resorption. PPi4- generated during the rolling circle amplification reaction acts as bisphosphonate analog and enhances bone targeting of Ca-polyCpG MDNs. In ovariectomized mouse and rabbit models, Ca-polyCpG MDNs prevented bone resorption and promoted bone repair by restoring the osteoporotic microenvironment, providing valuable insights into osteoporosis therapy.
Subject(s)
Bone Resorption , Nanoparticles , Osteoporosis , Mice , Animals , Rabbits , Osteoclasts/metabolism , Osteogenesis/genetics , Bone Resorption/drug therapy , Osteoporosis/drug therapy , Osteoporosis/metabolism , Cell DifferentiationABSTRACT
Fifty 3-month-old male Tan lambs (similar in body weight) were divided into 5 groups to investigate the effects of different restricted pasture grazing times and indoor supplementation on the productive performances and fatty acid composition of the intramuscular fat in growing lambs. The lambs grazed for different periods of time (12 h/d, 8 h/d, 4 h/d, 2 h/d, and 0 h) and received various amounts of supplementary feedings during the 120-day trial. Pasture dry matter intake (DMI), total DMI, average daily gains and the live body weights of the lambs were measured during the experiment. The animals were slaughtered at the end of the study, their carcass traits were measured, and their longissimus dorsi muscles were sampled to analyze the intramuscular fat (IMF) content and fatty acid profiles. The results indicated that the different durations of grazing and supplementary feedings affected the animal performances and the composition of fatty acids. Grazing for 8 h/d or 2 h/d with the corresponding supplementary concentrate resulted in lambs with higher body weights, carcass weights and IMF contents. Lambs with longer grazing times and less concentrate accumulated more healthy fatty acids such as conjugated linoleic acid and n-3 polyunsaturated fatty acid and had higher n-3/n-6 ratios. Overall, a grazing allowance of 8 h/d and the corresponding concentrate was recommended to maintain a high quantity and quality of lamb meat.