Passive and specific targeting of lymph nodes: the influence of the administration route

Abstract

Abstract:Patients diagnosed with an advanced-stage cancer present a dismal prognosis due to the presence of metastases. From the primary tumor, the cancer cells are disseminated via lymphatic circulation; metastases develop initially in lymph nodes. Therefore, the targeting of lymph nodes needs to be improved in the design of future chemotherapy, and one way to ensure this targeting is by using the subcutaneous (SC) route. Using lipid nanocapsules (LNCs) (40 nm and fluorescently-labeled with DiD) as nanocarriers, a correlation between the SC injection site (behind the neck, the right and left flanks, and above the tail) for LNC administration and specific lymph node accumulation (left and right cervical, axillary and inguinal lymph nodes) was achieved for SpragueDawley rats. The pharmacokinetic and biodistribution profiles confirmed the absence of LNCs in systemic circulation after SC administration due to the optimal size of the LNCs. With appropriate SC administration, LNCs can accumulate in specific lymph nodes, whereas IV administration led to a weak accumulation of LNCs in all lymph nodes. Specific accumulation followed the lymph flow: bottom-up from the lower to upper limbs and top down from the head, with two lymph circulation partitions: right upper limb and the rest. Administration above the tail presented high inguinal and axillary lymph node accumulation whereas weak accumulation was observed after administration behind the neck. LNCs administered in the left flank only accumulated in the left inguinal and axillary lymph nodes, whereas left and right inguinal and axillary lymph nodes presented accumulation after administration in the right flank. Cervical lymph nodes, in the opposite direction of lymph flow, were never targeted after SC administration, whatever the injection site.

A 3D-printed multi-compartment organ-on-chip platform with a tubing-free pump models communication with the lymph node

“…injection. 73 To test this hypothesis, we loaded a biotinylated model tissue into one of the tissue wells and injected NRho into an upstream compartment that was connected either through the pump well (well first, approximating i.v. injection) or directly through a microchannel (channel first, approximating s.c. or i.m.…”

Salmonella immunotherapy engineered with highly efficient tumor antigen coating establishes antigen-specific CD8+ T cell immunity and increases in antitumor efficacy with type I interferon combination therapy

“…After changing the injection to the tumor side, we observed better tumor control in the Sal-9RE7 treatment group. This can be due to Salmonella at the tumor-draining lymph node to target migratory dendritic cells and prime T cells for tumor infiltration, 30 , 31 while direct engagement of tumor draining lymph node that develops robust anti-tumor immunity. 32 Inflammation from the initial Sal-9RE7 dose cleared within days with little adverse effect on the mice.…”

Tolerogenic Nanovaccine for Prevention and Treatment of Autoimmune Encephalomyelitis

“…The greater lymphatic flow in the left side may explain the higher accumulation of nanoparticles in the left inguinal lymph node. [19] Flow cytometry revealed that the population of Cy5-positive DC was greater in the AbaLDPN-MOG group than in the LDPN-MOG group (Figure 4D; Figure S9, Supporting Information). Compared to LDPN-MOG (Figure 4E), AbaLDPN-MOG (Figure 4F) showed higher distribution throughout the lymph node.…”