About

Xin Li is a Professor in the Department of Electrical and Computer Engineering at Duke University. He received his Ph.D. in Electrical and Computer Engineering from Carnegie Mellon University in 2005, and his M.S. and B.S. degrees in Electronics Engineering from Fudan University in Shanghai, China, in 2001 and 1998, respectively. His research interests include integrated circuits, signal processing, and data analytics. He has held significant roles such as co-founding Xigmix Inc. to commercialize his Ph.D. research, serving as its Chief Technical Officer until its acquisition by Extreme DA, which was further acquired by Synopsis. He has also contributed to national research initiatives, including serving as Assistant Director for the FCRP Focus Research Center for Circuit & System Solutions (C2S2) and the Center for Silicon System Implementation (CSSI) at Carnegie Mellon University. Xin Li has been recognized with numerous awards, including the NSF CAREER Award and multiple Best Paper Awards from prestigious conferences. He has also served as an associate editor for several IEEE and ACM journals and has been involved in various professional committees and leadership roles within the research community.

Research topics

• Medicine
• Chemistry
• Pharmacology
• Biophysics
• Biochemistry
• Internal medicine
• Materials science
• Nanotechnology
• Biology
• Immunology
• Organic chemistry
• Combinatorial chemistry

Selected publications

• Intrinsically Disordered Protein Coating for Oral Delivery of Peptide Drugs

  Cell Biomaterials · 2025-10-24 · 1 citations

  preprintOpen access
  PublisherOA PDFDOI

• Spatiotemporal Control of IL‐12 Delivery Improves Its Efficacy in Treatment of Solid Tumors

  Advanced Therapeutics · 2025-07-16

  article

  Abstract Despite renewed interest in IL‐12 as a cancer immunotherapy due to its ability to stimulate the adaptive immune system, its short half‐life and narrow therapeutic window continues to present challenges for effective delivery. Previous studies with IL‐12 have investigated the effects of route of delivery or sustained delivery of the cytokine on its efficacy but are unable to simultaneously investigate the effects of both within the same system. This work seeks to address this gap by utilizing an elastin‐like polypeptide (ELP) carrier, which can undergo a thermally triggered phase transition to a gel‐like depot, to probe the effects of both sustained release and spatial delivery of IL‐12. By conjugating IL‐12 with an ELP, this work creates an IL‐12‐ELP fusion that can be injected intratumorally or subcutaneously to form a sustained‐release depot. In a B16F10 murine model, intratumoral injection of a depot‐forming IL‐12‐ELP fusion significantly improved survival compared to free IL‐12. IL‐12‐ELP is retained within the tumor approximately fourfold longer than free IL‐12, resulting in higher CD8+ T cell recruitment at the tumor and local concentrations of inflammatory cytokines at Day 2. Taken together, this work provides insights into rational cytokine delivery, the importance of tumor localization, and the benefits of sustained release.

  PublisherDOI

• Controlling Release Kinetics of an Adjuvant from a Depot Improves the Efficacy of Local Immunotherapy in Metastatic Cancer

  Advanced Science · 2025-07-06 · 5 citations

  articleOpen access

  Abstract Biomaterials can improve cancer immunotherapies by controlling their release and thereby optimizing their time‐dependent engagement of the immune system. In this study, an approach is described to control the release of a potent immunostimulant—CpG oligodeoxynucleotide—from a genetically‐encoded elastin‐like polypeptide (ELP) depot. A CpG‐binding ELP containing an oligolysine domain (ELP‐Lys 12 ) is synthesized that electrostatically complexes CpG and formulate it with an excipient ELP. The ELP‐CpG complex retains the thermally responsive phase behavior of the parent ELP, transitioning into a viscous depot at body temperature. Stepwise addition of excipient ELP predictably changes ELP‐CpG transition temperature, depot dissolution kinetics, and retention of CpG within the depot. Mixtures of ELP‐Lys 12 , excipient ELP, and CpG undergo microphase separation, forming a porous, sponge‐like depot that contains tunable amounts of soluble CpG in the pores. In vivo, the modified formulations exhibit varying degrees of CpG retention over multiple weeks following a single intratumoral injection. Finally, by modifying the release kinetics of CpG, optimized ELP‐CpG achieves greater reduction of metastatic disease in a murine metastatic breast cancer model than soluble CpG. These results demonstrate that ELPs can be used to precisely tune the release kinetics of immunotherapies for better outcomes in the treatment of metastatic cancer.

  PublisherOA PDFDOI

• Binding Strength, Not Valency, Dictates Accumulation and Penetration of Affinity Targeted Macromolecules into Solid Tumors

  Biomacromolecules · 2024-12-27

  article

  The efficacy of tumor-targeted therapeutics, engineered to engage specific cellular receptors to promote accumulation and penetration, is strongly influenced by the carrier's affinity for its target and the valency of binding molecules incorporated into the carrier. Previous research has primarily focused on improving targeting by augmenting the number of binding proteins on the carrier, inadvertently raising avidity without isolating the individual effects of binding strength and valency. Herein, we precisely evaluate the impact of multivalency on tumor targeting with a recombinant approach to independently control valency, avidity, and size. Our findings reveal that constructs with equivalent binding strength exhibit comparable receptor engagement and tumor extravasation, regardless of valency. Moreover, excessive avidity adversely affected tumor accumulation and penetration, with the highest-avidity construct showing diminished exposure. These results indicate that overall binding strength, not valency, is the primary determinant of tumor targeting, providing valuable insights for designing effective macromolecular drug carriers.

  PublisherDOI

• Preclinical Development of a Genetically Engineered Albumin‐Binding Nanoparticle of Paclitaxel

  Small Science · 2024-09-25 · 8 citations

  articleOpen access

  Nab-paclitaxel (Abraxane), an albumin-bound solvent-free paclitaxel (PTX) formulation that takes advantage of the endogenous albumin transport pathway, is the current gold standard for treatment of solid tumors with PTX. However, nab-paclitaxel has several limitations, including complex manufacturing, immunogenicity, slow drug-release, and a narrow therapeutic window. Nevertheless, no other PTX formulation has gained the Food and Drug Administration approval since Abraxane's 18-year reign. Addressing these concerns, herein, a PTX-loaded nanoparticle of a recombinant polypeptide that-like nab-paclitaxel-capitalizes on the long in vivo half-life of albumin is reported. This genetically engineered nanoparticle packages PTX in the core of the nanoparticle and displays an albumin-binding domain on the exterior of the nanoparticle. Upon in vivo administration, the drug-loaded nanoparticle binds albumin with nanomolar affinity, and acquires an albumin-corona, which eliminates the need to use exogenous albumin. The nanoparticles can be stored at subzero temperature as lyophilized powder without any cryoprotectants for upto a year and can be reconstituted on-demand in aqueous buffer at high concentration, thus greatly simplifying formulation processes. These albumin-binding nanoparticles improve the therapeutic window by at least twofold compared to nonalbumin-binding counterpart and outperform nab-paclitaxel in multiple murine tumor models, results that have been independently replicated by a contract research organization.

  PublisherOA PDFDOI

• An injectable PEG-like conjugate forms a subcutaneous depot and enables sustained delivery of a peptide drug

  Biomaterials · 2023-01-03 · 24 citations

  articleOpen access
  PublisherOA PDFDOI

• Brachytherapy via a depot of biopolymer-bound 131I synergizes with nanoparticle paclitaxel in therapy-resistant pancreatic tumours

  Nature Biomedical Engineering · 2022-10-19 · 39 citations

  articleOpen access
  PublisherOA PDFDOI

• Genetically Engineered Nanoparticles of Asymmetric Triblock Polypeptide with a Platinum(IV) Cargo Outperforms a Platinum(II) Analog and Free Drug in a Murine Cancer Model

  Nano Letters · 2022 · 11 citations

  • Materials science
  • Combinatorial chemistry
  • Chemistry

  The development of platinum(Pt)-drugs for cancer therapy has stalled, as no new Pt-drugs have been approved in over a decade. Packaging small molecule drugs into nanoparticles is a way to enhance their therapeutic efficacy. To date, there has been no direct comparison of relative merits of the choice of Pt oxidation state in the same nanoparticle system that would allow its optimal design. To address this lacuna, we designed a recombinant asymmetric triblock polypeptide (ATBP) that self-assembles into rod-shaped micelles and chelates Pt(II) or enables covalent conjugation of Pt(IV) with similar morphology and stability. Both ATBP-Pt(II) and ATBP-Pt(IV) nanoparticles enhanced the half-life of Pt by ∼45-fold, but ATBP-Pt(IV) had superior tumor regression efficacy compared to ATBP-Pt(II) and cisplatin. These results suggest loading Pt(IV) into genetically engineered nanoparticles may yield a new generation of more effective platinum-drug nanoformulations.

  PublisherOA PDFDOI

• Intratumoral delivery of brachytherapy and immunotherapy by a thermally triggered polypeptide depot

  Journal of Controlled Release · 2022-01-22 · 33 citations

  articleOpen access
  PublisherOA PDFDOI

• P2RY2-AKT activation is a therapeutically actionable consequence of XPO1 inhibition in acute myeloid leukemia

  Nature Cancer · 2022-06-06 · 42 citations

  articleOpen access
  PublisherOA PDFDOI

Frequent coauthors

• Ashutosh Chilkoti

  Duke University

  60 shared

• Jeffrey L. Schaal

  Pratt Institute

  24 shared

• Ivan Spasojević

  20 shared

• Jayanta Bhattacharyya

  19 shared

• Wenge Liu

  Baidu (China)

  19 shared

• Samagya Banskota

  Duke University

  17 shared

• Soumen Saha

  Duke University

  15 shared

• Nikita Zakharov

  Pratt Institute

  15 shared

Awards & honors

• Fellow. Institute of Electrical and Electronics Engineers (2…
• IEEE Donald O. Pederson Best Paper Award (2016)
• IEEE Donald O. Pederson Best Paper Award (2013)
• Best Paper Award from Design Automation Conference (2010)
• IEEE/ACM William J. McCalla ICCAD Best Paper Award (2011)