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External temperature control of lymphatic drainage of thermo-sensitive nanomaterials

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Abstract

Nano-carrier-facilitated delivery of bioactive molecules into lymph nodes (LNs) has found application in the treatment and diagnosis of numerous immune-related diseases. Much work has focused on optimization of physicochemical properties of the nano-carrier to enhance lymphatic drainage passively, whereas active modulation of the quantity and timing of lymphatic delivery remains a significant challenge. Here, inspired by the success of thermo-modulation of tumor targeting, we have developed a simple external temperature control strategy to regulate the distribution of thermo-sensitive nanomaterials between the injection site and draining LNs. To demonstrate feasibility of this strategy, we injected Rhodamine-B-labeled poly(N-isopropylacrylamide) (RhB-PNIPAm) (2.5 kDa) into the footpad of mice at different initial temperatures – either below or above the lower critical solution temperature (LCST), followed by physical cooling of the injection site. We show that RhB-PNIPAm drained efficiently into the popliteal and inguinal nodes (pLNs, iLNs, respectively) with low levels of accumulation in major internal organs. Within the first two hours post-injection the rate of drainage was primarily dependent on the initial temperature of RhB-PNIPAm. However, over the course of 24 h, temperature gradient due to local cooling affected significantly the draining of the injection site, resulting in differential accumulation of RhB-PNIPAm in the proximal (pLNs) versus the distal (iLNs) nodes. This study provides a new methodology and insights for modulating in vivo lymphatic distribution of thermo-sensitive nanomaterials with implications in immune regulation and immunotherapy.

Graphical abstract: External temperature control of lymphatic drainage of thermo-sensitive nanomaterials

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Publication details

The article was received on 15 Oct 2018, accepted on 28 Nov 2018 and first published on 29 Nov 2018


Article type: Paper
DOI: 10.1039/C8BM01298A
Citation: Biomater. Sci., 2019, Advance Article
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    External temperature control of lymphatic drainage of thermo-sensitive nanomaterials

    M. Zhang, W. Chen, Y. Hong, H. Chen and C. Wang, Biomater. Sci., 2019, Advance Article , DOI: 10.1039/C8BM01298A

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