Abstract
In preclinical studies of young mice, nanoparticles showed excellent anti-tumor therapeutic effects by harnessing Peripheral Blood Monocytes (PBMs) and evading the immune system. However, the changes of age will inevitably affect PBMs and the immune system, and there is a serious lack of relevant research. Sialic acid (SA)-octadecylamine (ODA) was synthesized, and SA- or polyethylene glycol (PEG)-modified epirubicin (EPI) liposomes (EPI-SL and EPI-PL, respectively) were prepared to explore differences in antitumor treatment using 8-month-old and 8-week-old Kunming mice. Based on presented data, 8-month-old mice had more PBMs in peripheral blood than 8-week-old mice, and age differences resulted in different anti-tumor treatment effects following EPI-SL and EPI-PL treatment. Following EPI-PL administration, the tumor volume was significantly smaller in 8-week-old mice than in 8-month-old mice (* p < 0.05). Eight-month-old mice treated with EPI-SL (8M-SL) presented no damage to healthy tissue, with a 100% survival rate, and 50% mice in 8M-SL showed ‘shedding’ of tumor tissues from the growth site. Accordingly, 8-month-old mice treated with EPI-SL achieved the best therapeutic effect at different ages and with different liposomes. EPI-SL could improve the antitumor effect of 8-week-old and 8-month-old mice.
Highlights
Older individuals, those that are frail or those living in long-term care facilities, are disproportionately affected by diseases, and the aging of tissues in the body has serious effects on therapy [1–3] as aging leads to a series of degenerative changes in the function and number of innate immune cells [4]
We investigated the effects of Sialic acid (SA), polyethylene glycol (PEG), and age on liposome distribution in vivo
nuclear magnetic resonance (NMR) (CD3OD, dppm), 3.93 (2H, H-6, H-4), 3.71 (2H, H-9, H-5), 3.58 (2H, H-90, H-8), 3.21 (1H, H-7), 3.10 (2H, H-1), 2.19 (1H, H-30), 1.92 (3H, H-10), 1.43 (1H, H-3), 1.19 (30H, alkyl), and 0.8 (3H, H-11) were identified (Figure 1A). These results confirmed the successful synthesis of SA-ODA
Summary
Those that are frail or those living in long-term care facilities, are disproportionately affected by diseases (especially cancer), and the aging of tissues in the body has serious effects on therapy [1–3] as aging leads to a series of degenerative changes in the function and number of innate immune cells (monocytes, macrophages, etc.) [4]. Doxil® was the first marketed liposomal product using the enhanced permeability and retention (EPR) effect of tumor sites [13,14]. SA-modified liposomes are reportedly recognized by the Siglec-1 receptor on the monocyte surface, phagocytosed, and delivered to the tumor site through spontaneous migration [19]. This strategy increases drug accumulation in the tumor, destroys the tumor immunosuppressive state, and enhances infiltration of PBMs (some mice even shed tumors). Significant differences in tumor molecular characteristics between patient populations of different ages can lead to a decrease in the anti-therapeutic effect of nanoparticles. 8-month-old Kunming mice exhibited superior therapeutic efficacy, less hair loss, and minimal tissue damage following EPI-SL treatment when compared with mice administered EPI-PL
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