Intranodal delivery of modified docetaxel: Innovative therapeutic method to inhibit tumor cell growth in lymph nodes

Sukhbaatar, Ariunbuyan; Mori, Shiro; Kodama, Tetsuya

doi:10.1111/cas.15283

Cited by 8 publications

(15 citation statements)

References 65 publications

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“… 36 Direct administration of CDDP into LNs by LDDS is an effective method to increase bioavailability in LNs and to induce immunogenic cell stress. 14 , 16 …”

Section: Discussionmentioning

confidence: 99%

“…The LDDS is a local treatment method in which anticancer drugs are injected directly into LNs to target early metastases. 14 , 15 , 16 The LDDS produces a higher drug retention rate and tissue selectivity in LNs compared to systemic chemotherapy and elicits greater antitumor effects. 14 , 16 Assuming clinical application, the amount of drug used is extremely low (1/1000–10,000 of systemic chemotherapy), and side‐effects are minimal.…”

Section: Introductionmentioning

confidence: 99%

“… 14 , 15 , 16 The LDDS produces a higher drug retention rate and tissue selectivity in LNs compared to systemic chemotherapy and elicits greater antitumor effects. 14 , 16 Assuming clinical application, the amount of drug used is extremely low (1/1000–10,000 of systemic chemotherapy), and side‐effects are minimal. Recently, it has been shown that the antitumor effect can be further enhanced by adjusting the anticancer drugs used in LDDS with a highly osmotic, highly viscous solvent.…”

Section: Introductionmentioning

confidence: 99%

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Combination therapy of lymphatic drug delivery and total body irradiation in a metastatic lymph node and lung mouse model

et al. 2022

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Chemotherapy using a lymphatic drug delivery system (LDDS) targeting lymph nodes (LNs) in the early stage of metastasis has a superior antitumor effect to systemic chemotherapy. An LDDS produces a higher drug retention rate and tissue selectivity in LNs. To expand the therapeutic coverage of LDDS from local treatment of metastatic LNs to prevention of distant metastases, the combination of treatment with therapies that enhance systemic tumor immune effects is an important therapeutic strategy. Recently, total body irradiation (TBI) has been shown to activate immune responses and alter the tumor microenvironment. Here we show that combination therapy with TBI and LDDS improves the antitumor effect of metastatic LNs and lung metastasis. Tumor cells were inoculated into the subiliac LN (SiLN) to induce metastasis into the proper axillary LN (PALN) and lung in a mouse model. TBI was carried out on day 4 after inoculation using a gamma irradiator. Lymphatic drug delivery into the accessory axillary LN was used to treat PALN. In vivo bioluminescence imaging, high‐frequency ultrasound, and histology showed that combination therapy using TBI (total dose 1.0 Gy once) and the LDDS suppressed tumor growth in LNs and lung metastases and was more effective than using LDDS or TBI alone. Quantitative RT‐PCR of spleens after combination therapy revealed increased expression of CD4 , CD8 , and IL‐12b , indicating an activated immune response. The results show that combination therapy with TBI and LDDS is a method to improve the efficacy of LN metastases and distant metastases therapy and is a promising novel approach to treat cancer patients.

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“… 36 Direct administration of CDDP into LNs by LDDS is an effective method to increase bioavailability in LNs and to induce immunogenic cell stress. 14 , 16 …”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Combination therapy of lymphatic drug delivery and total body irradiation in a metastatic lymph node and lung mouse model

et al. 2022

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“…Mainstay chemotherapeutic agents such as cisplatin and fluorouracil (5‐FU), administered through the LDDS in a murine model of LN metastasis, have shown superior tumor inhibition compared to their systemic administration in the same model. 16 , 18 , 19 , 20 While the LDDS addresses certain limitations of systemic chemotherapy, and exerts a stronger antitumor effect, further fine‐tuning is mandated for potentiation of the beneficial antitumor effects.…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies undertaken by our group, using cisplatin and docetaxel, have touched on and verified the impact of solvent osmotic pressure and viscosity on anticancer effect elicited by chemotherapeutic agents in the context of MLNs. 19 , 20 However, while these studies have highlighted the importance of these parameters, osmotic pressure and viscosity have not been independently investigated. This study was designed to evaluate the individual contributions of elevated osmotic pressure and viscosity on the therapeutic response and to establish an optimized window of solvent osmotic pressure and viscosity for treatment of MLNs using the LDDS.…”

Section: Introductionmentioning

confidence: 99%

Drug formulation augments the therapeutic response of carboplatin administered through a lymphatic drug delivery system

et al. 2022

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Treatment of metastatic lymph nodes (LNs) is challenging due to their unique architecture and biophysical traits. Systemic chemotherapy fails to impede tumor progression in LNs due to poor drug uptake and retention by LNs, resulting in fatal systemic metastasis. To effectively treat LN metastasis, achieving specific and prolonged retention of chemotherapy drugs in the tumor‐draining LNs is essential. The lymphatic drug‐delivery system (LDDS) is an ultrasound‐guided drug‐delivery methodology for administration of drugs to LNs that addresses these requirements. However, early‐stage metastatic LNs have an additional set of drug transport barriers, such as elevated intranodal pressure and viscosity, that negatively impact drug diffusion. In the present study, using formulations of elevated osmotic pressure and viscosity relative to saline, we sought to favorably alter the LN's physical environment and study its impact on pharmacokinetics and consequently the therapeutic efficacy of carboplatin delivered using the LDDS. Our study confirmed the capability of a drug formulation with elevated osmotic pressure and viscosity to alter the architecture of LNs, as it caused notable expansion of the lymphatic sinus. Additionally, the study delineated an optimal range of osmotic pressure and viscosity, centered around 1897 kPa and 11.5 mPa·s, above and below which therapeutic efficacy was found to decline markedly. These findings suggest that formulation osmotic pressure and viscosity are parameters that require critical consideration as they can both hinder and promote tumorigenesis. The facile formulation reported here has wide‐ranging applicability across cancer spectrums and is thus anticipated to be of great clinical benefit.

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Dendritic Cell‐Hitchhiking In Vivo for Vaccine Delivery to Lymph Nodes

Zhou,

Zhao,

Wang

et al. 2024

Advanced Science

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Therapeutic cancer vaccines are among the first FDA‐approved cancer immunotherapies. Among them, it remains a major challenge to achieve robust lymph‐node (LN) accumulation. However, delivering cargo into LN is difficult owing to the unique structure of the lymphatics, and clinical responses have been largely disappointing. Herein, inspired by the Migrated‐DCs homing from the periphery to the LNs, an injectable hydrogel‐based polypeptide vaccine system is described for enhancing immunostimulatory efficacy, which could form a local niche of vaccine “hitchhiking” on DCs. The OVA peptide modified by lipophilic DSPE domains in the hydrogel is spontaneously inserted into the cell membrane to achieve “antigen anchoring” on DCs in vivo. Overall, OVA peptide achieves active access LNs through recruiting and “hitchhiking” subcutaneous Migrated‐DCs. Remarkably, it is demonstrated that the composite hydrogel enhances LNs targeting efficacy by approximately six‐fold compared to free OVA peptide. Then, OVA peptide can be removed from the cell surface under a typical acidic microenvironment within the LNs, further share them with LN‐resident APCs via the “One‐to‐Many” strategy (One Migrated‐DC corresponding to Many LN‐resident APCs), thereby activating powerful immune stimulation. Moreover, the hydrogel vaccine exhibits significant tumor growth inhibition in melanoma and inhibits pulmonary metastatic nodule formation.

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Intranodal delivery of modified docetaxel: Innovative therapeutic method to inhibit tumor cell growth in lymph nodes

Cited by 8 publications

References 65 publications

Combination therapy of lymphatic drug delivery and total body irradiation in a metastatic lymph node and lung mouse model

Combination therapy of lymphatic drug delivery and total body irradiation in a metastatic lymph node and lung mouse model

Drug formulation augments the therapeutic response of carboplatin administered through a lymphatic drug delivery system

Dendritic Cell‐Hitchhiking In Vivo for Vaccine Delivery to Lymph Nodes

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