# LIPOSOME-MEDIATED INTRACELLULAR DELIVERY IN VITRO

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 1987 · $149,358

## Abstract

We are proposing to develop new methods for optimal delivery of cytotoxic
drugs and other macromolecules to specific tumor cells in vitro, by the use
of antibody-targeted liposomes.  We have planned a three-pronged approach
which involves both the development of new liposome systems and their
application to specifically-selected tumor cells.

1. pH-sensitive, fusogenic liposomes:  We are planning to optimize the
behaviour of pH-sensitive liposomes for obtaining maximal cytoplasmic
release following endocytosis.  Specifically, we will accomplish this goal
by:  (a) formulation of appropriate fatty-acid/phosphatidylethanolamine
(FA/PE) liposomes that fuse without leakage by avoiding the Hexagonal phase
transition of PE; (b) synthesis of new pH-sensitive lipids of appropriate
molecular architecture.  The extent of cytoplasmic release will be followed
by fluorescent probes, inhibition of protein synthesis by toxin A fragments
and infectivity of viral DNA.

2. New Assays for endocytosis and lysosomal processing:  Liposomes will be
used as carriers of fluorescent or fluorogenic molecules capable of
responding either to low pH or to the presence of specific hydrolytic
enzymes.  To achieve this we will use the following types of probes:  (a)
fluorescent probes that show an easily measurable pH-induced spectral
shift; (b) fluorogenic probes that show an easily measurable pH-induced
spectral shift; (b) fluorogenic probes attached to liposome-encapsulated
ligands via a pH-sensitive covalent bond; (c) fluorogenic probes attached
by a bond cleavable by specific enzymes, by elastase, or other proteases.

Judicious use of such assays will give valuable quantitative information on
the kinetics of endocytosis andphage-lysosome fusion applicable both to
drug delivery via liposomes but also to studies on the fate of pathogenic
viruses and bacteria.

3. Targeting to specific tumor cells:  We have selected as model systems
human (ovarian carcinoma) and murine (liver metastatic) tumor cell lines
for specific reasons relating to intended future therapeutic applications
in animals and ultimately in humans.  We plan to maximize the cytotoxicity
of drug-loaded liposomes by using targeted liposomes that have the
necessary properties for efficient cytoplasmic delivery of the encapsulated
drug.

## Key facts

- **NIH application ID:** 3172917
- **Project number:** 5R01CA035340-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **SAM.gov UEI:** KMH5K9V7S518
- **Principal Investigator:** DEMETRIOS D PAPAHADJOPOULOS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $149,358
- **Award type:** 5
- **Project period:** 1983-07-01 → 1989-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172917

## Citation

> US National Institutes of Health, RePORTER application 3172917, LIPOSOME-MEDIATED INTRACELLULAR DELIVERY IN VITRO (5R01CA035340-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3172917. Licensed CC0.

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