Nanofluidic drug-eluting seed for sustained intratumoral immunotherapy in triple negative breast cancer

Emerging Technologies for Local Cancer Treatment

“…Building upon this research, Chua et al performed efficacy studies in the 4T1 mouse model of triple negative breast cancer to determine the effect of intratumoral immunotherapy release on tumor control. [55] Intratumoral release of CD40 antibody via the nanofluidic drug-eluting seed showed enhanced inhibition of tumor growth with minimal systemic toxicity as compared to conventional systemic treatment. Envisioned to be utilized as a drug-eluting platform for delivering neoadjuvant therapy intratumorally, the nanofluidic drug-eluting seed could fulfill the unmet need for an approach that maximizes tumor drug exposure and eliminates repeated injections.…”

“…Active therapeutic Type of cancer Year Reference Chemotherapy PLLA/PEG4000 implant Etoposide NSCLC 2017 [40] In situ gel-forming PCL-PEG-PCL hydrogel implant Liposomal doxorubicin/rhenium-188-tin colloid HCC 2013 [41] PEG nanotubes Doxorubicin Breast 2018 [42] Liquid crystal polymer microcapsule Temozolomide/doxorubicin Brain metastasis 2014 [43] Lauroyl-gemcitabine nanocapsule hydrogel Gemcitabine Glioblastoma 2016 [44] Iontophoretic delivery Gemcitabine/FOLFIRINOX Regimen Breast/pancreas 2015/2016 [ 45,46] Iontophoretic delivery EGFR-targeted liposomal 5-FU SCC 2018 [47] Immunotherapy pLHMGA microparticles CD40 antibody/ CTLA4 antibody Colon carcinoma 2015 [48] Dextran/PLGA-PLA core/shell microspheres IL-2 Colon carcinoma 2013 [49] Injectable collagen-anchoring cytokines IL-2/IL-12 Melanoma/breast/colon 2019 [50] Injectable bio-responsive gel PD-L1 antibody /d-1MT Melanoma 2018 [51] Injectable alginate hydrogel Imiquimod and anti-PD-L1 with doxorubicin or oxaliplatin Breast/colon/glioma 2020 [52] Smart radiotherapy biomaterial PLGA matrix CD40 antibody/radiation NSCLC 2018 [53] Transcutaneous microneedle Patch PD1 antibody Melanoma 2016 [54] Nanofluidic drug eluting seed CD40 antibody / OX40 antibody Breast 2018 [55] Radiotherapy Radiation-linked polypeptide hydrogel depot Iodine-131 Prostate/pancreas 2016 [56] Iodine-131 CpG/ CTLA4 antibody Breast/prostate/colon/liver 2018 [57] EGFR-targeted radioactive gold nanoparticles Panitimumab and lutetium-177 Breast 2015 [58] NBTXR3…”

“…Moving beyond microfluidic platforms, one promising nanofluidic-based approach is a drug-eluting seed for intratumoral release of anticancer drugs including immunotherapy developed by the authors' group ( Figure 3D). [125,55] The nanofluidic implant is smaller in size than a grain of rice and is inserted intratumorally using a minimally invasive clinical trocar approach, similar to brachytherapy seed insertion. Drug elution occurs through a nanofluidic membrane mounted on the reservoir, in which various types of agents could be delivered.…”

Improved Efficacy of Antibody Cancer Immunotherapeutics through Local and Sustained Delivery

“…Intratumoral injectiono fan anofluidic implant that released an anti-CD40 monoclonala ntibody in a4 T1 mouseb reast cancer model increased Tcell infiltration into tumors and decreasedo ft umor volume by 50 %w hen compared to untreated controlsa fter 14 days. [92] Systemic administration of the anti-CD40 antibody also reduced tumor volume, butr esulted in hepatocellular damage.S ustainedl ocal delivery of a3 0mg anti-CD40 antibody dose from ad egradable drug depot( Montanide ISA-51) increased systemic CTL response in an AR6 mouse tumor modelt oasimilar level and efficacy as 100 mgI V doses (> 50 %s urvival of mice after 70 days);l ocal delivery resulted in alower degree of liver damage. [93]…”

“…Intratumoral injection of a nanofluidic implant that released an anti‐CD40 monoclonal antibody in a 4T1 mouse breast cancer model increased T cell infiltration into tumors and decreased of tumor volume by 50 % when compared to untreated controls after 14 days . Systemic administration of the anti‐CD40 antibody also reduced tumor volume, but resulted in hepatocellular damage.…”