Current interstitial therapies for glioblastoma can overcome the blood−brain barrier but fail to optimally release therapy at a rate that stalls cancer reoccurrence. To address this lapse, acetalated dextran (Ace-DEX) nanofibrous scaffolds were used for their unique degradation rates that translate to a broad range of drug release kinetics. A distinctive range of drug release rates was illustrated via electrospun Ace-DEX or poly(lactic acid) (PLA) scaffolds. Scaffolds composed of fast, medium, and slow degrading Ace-DEX resulted in 14.1%, 2.9%, and 1.3% paclitaxel released per day. To better understand the impact of paclitaxel release rate on interstitial therapy, two clinically relevant orthotopic glioblastoma mouse models were explored: (1) a surgical model of resection and recurrence (resection model) and ( 2) a distant metastasis model. The effect of unique drug release was illustrated in the resection model when a 78% long-term survival was observed with combined fast and slow release scaffolds, in comparison to a survival of 20% when the same dose is delivered at a medium release rate. In contrast, only the fast release rate scaffold displayed treatment efficacy in the distant metastasis model. Additionally, the acidsensitive Ace-DEX scaffolds were shown to respond to the lower pH conditions associated with GBM tumors, releasing more paclitaxel in vivo when a tumor was present in contrast to nonacid sensitive PLA scaffolds. The unique range of tunable degradation and stimuli-responsive nature makes Ace-DEX a promising drug delivery platform to improve interstitial therapy for glioblastoma.

The primary cause of mortality for glioblastoma (GBM) is local tumor recurrence following standard-of-care therapies, including surgical resection. With most tumors recurring near the site of surgical resection, local delivery of chemotherapy at the time of surgery is a promising strategy. Herein drug loaded polymer scaffolds with two distinct degradation profiles were fabricated to investigate the effect of local drug delivery rate on GBM recurrence following surgical resection. The novel biopolymer, acetalated dextran (Ace-DEX), was compared to commercially available polyester, poly(L-lactide) (PLA). Steady state doxorubicin (DXR) release from Ace-DEX scaffolds was found to be faster when compared to scaffolds comprised of PLA, in vitro. This increased drug release rate translated to improved therapeutic outcomes in a novel surgical model of orthotopic glioblastoma resection and recurrence. Mice treated with DXR loaded Ace-DEX scaffolds (Ace-DEX/10DXR) resulted in 57% long term survival out to study completion at 120 days compared to 20% survival following treatment with DXR loaded PLA scaffolds (PLA/10DXR). Additionally, all mice treated with PLA/10DXR scaffolds exhibited disease progression by day 38, as defined by a five-fold growth in tumor bioluminescent signal. In contrast, 57% of mice treated with Ace-DEX/10DXR scaffolds displayed a reduction in tumor burden, with 43% exhibiting complete remission. These results underscore the importance of polymer choice and drug release rate when evaluating local drug delivery strategies to improve prognosis for GBM patients undergoing tumor resection.

Judicious combination of semiconducting polymers with alternating electron donor (D) and acceptor (A) segments created hybrid nanoparticles with amplified energy transfer and red-shifted emission, while simultaneously providing photothermal capabilities. Hybrid D-A polymer particles (H-DAPPs) passively localized within orthotopic breast tumors, serving as bright fluorescent beacons. Laser stimulation induced heat generation on par with gold nanorods, resulting in selective destruction of the tumor. H-DAPPs can also undergo multiple thermal treatments, with no loss of fluorescence intensity or photothermal potential. These results indicate that H-DAPPs provide new avenues for the synthesis of hybrid nanoparticles useful in localized detection and treatment of disease.

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