# High throughput nanoplasmonic exosome testing (NEXT) of immunotherapies in bladder cancer

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $629,224

## Abstract

Challenges. Once metastatic, only 5 out of 100 patients are alive at ﬁve years. Immune checkpoint
inhibitors have demonstrated increasing clinical traction yet conventional imaging such as CT scans
struggle to accurately assess tumor response in this treatment context. Serially accessible sources of
tumor and host biomarkers could add earlier insights into response this informing timely go / no-go
decision making to render precision immunotherapy. Innovation: In light of needed pre-competitive
nanotechnology tools for EV investigation to ﬁll temporal and scientiﬁc gaps precluding accurate
immunotherapy-based treatment monitoring, our group developed and validated a magneto-
electrochemical platform without need for EV puriﬁcation and capable of 96 parallel readouts within
45 minutes. This proposal exploits the bladder's intimate anatomical location within the genitourinary
system; urine would thus provide us with rich repositories of bladder cancer EVs. We previously
demonstrated feasibility of urine EV testing in kidney transplant rejection. Through increased excited
charges generated by inducing plasmonic resonance in gold nanoparticles, we recently accelerated
electrochemical reactions within our most current and scalable platform to achieve 12-fold signal
increase from EV surface markers. We hypothesize that advancing our nanoplasmonic EV sensor for
human urine and optimizing assay protocols to measure intra-EV and surface markers, could identify
high value bladder cancer and host biomarkers (protein and mRNA) to better examine their interplay
over time and under treatment pressures. We propose three speciﬁc aim: AIM 1: To optimize our
nanoplasmonic sensor (NEXT) assay and instrumentation for high-throughput urine-based analyses
and comprehensive proﬁling of both surface and intra-EV markers. AIM 2: To employ pre-clinical and
banked biospecimens for NEXT analyses to examine proﬁling performance and inform optimal
biomarker panel. AIM 3: Use NEXT to prospectively monitor and proﬁle urinary EVs from patients
undergoing immunotherapy-based therapies for bladder cancer. Impact: Our highly complementary
group of accomplished investigators bring to bear longstanding expertise and translational experience
in EV biology, bioengineering, systems biology, bioinformatics, and clinical oncology. If successful, our
urinary nanoplasmonic EV platform would add critical actionable insights into immunotherapy-based
treatments of advanced bladder cancers with promise in other prevalent genitourinary cancers such
as kidney and prostate.

## Key facts

- **NIH application ID:** 10914815
- **Project number:** 5R01CA264363-04
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Cesar M Castro
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $629,224
- **Award type:** 5
- **Project period:** 2021-08-06 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10914815

## Citation

> US National Institutes of Health, RePORTER application 10914815, High throughput nanoplasmonic exosome testing (NEXT) of immunotherapies in bladder cancer (5R01CA264363-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10914815. Licensed CC0.

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