Introduction: The Next Frontier of Lipid Nanoparticles (LNPs) in Cancer Nanomedicine
For decades, cancer nanomedicine has pursued a central goal — to deliver potent therapies directly to tumors while sparing healthy tissues. Lipid nanoparticles (LNPs) have emerged as one of the most clinically validated nanocarriers, from mRNA delivery to small-molecule encapsulation. Yet, a new generation of lipid-based technologies is pushing the boundaries even further: theranostic lipid nanoparticles, capable of performing both diagnostic imaging and therapeutic intervention within a single platform.
At the recent BOC Sciences Webinar: “Theranostic Lipid Nanoparticles for Cancer Medicine”, Dr. Gang Zheng, Professor and Tier 1 Canada Research Chair in Cancer Nanomedicine at the University of Toronto and Associate Research Director at the Princess Margaret Cancer Centre, presented a comprehensive overview of how porphyrin-based lipid nanoparticles — or porphysomes — are redefining the future of precision oncology.
His presentation showcased nearly two decades of innovation, from basic photodynamic therapy (PDT) research to first-in-human clinical translation of radiolabeled theranostic nanoparticles. Dr. Zheng’s work exemplifies how integrating imaging and therapy can lead to safer, smarter, and more personalized cancer treatments.
What Are Theranostic Lipid Nanoparticles?
The word theranostic fuses “therapy” and “diagnostics,” describing nanostructures engineered to deliver drugs while simultaneously providing imaging signals that reveal their distribution, accumulation, and efficacy in real time.
In oncology, this concept offers transformative potential:
- Personalized medicine: By visualizing how nanoparticles behave inside a patient’s body, clinicians can optimize drug dosage and timing.
- Early response monitoring: Imaging readouts reveal therapeutic success or resistance before clinical symptoms appear.
- Reduced systemic toxicity: Targeted delivery and real-time imaging minimize off-target exposure.
Lipid nanoparticles are particularly well-suited for theranostics. Composed of biocompatible phospholipids and cholesterol, they mimic biological membranes and can encapsulate both hydrophilic and hydrophobic payloads. Their surface can also be functionalized with imaging probes, targeting ligands, or radionuclides, making them highly adaptable.
As Dr. Zheng emphasized, “Most clinically approved or investigational nanomedicines are lipid-based — they provide the right balance of biocompatibility, flexibility, and manufacturing scalability.”
Porphysomes: Nature-Inspired Theranostic Lipid Nanoparticles
At the heart of Dr. Zheng’s research is the porphysome, a self-assembled lipid nanoparticle constructed from porphyrin-lipid conjugates. Porphyrins are naturally occurring pigments — essential for oxygen transport and photosynthesis — that also possess unique photophysical properties, including fluorescence, light absorption, and metal chelation.
When porphyrin-lipids are packed into a bilayer, they form porphysomes, exhibiting:
- High optical absorption and fluorescence quenching — ideal for photothermal therapy (PTT);
- Efficient heat conversion, enabling photoacoustic imaging (PAI);
- Reversible fluorescence activation, allowing switchable photodynamic therapy (PDT).
This multifunctionality means a single nanoparticle can image, treat, and report therapeutic outcomes — an all-in-one nanotheranostic system.
In animal studies, porphysomes have demonstrated exceptional tumor accumulation and selective photoactivation. Upon local illumination, the quenched porphyrins become fluorescent and cytotoxic, producing reactive oxygen species (ROS) that kill cancer cells with minimal damage to surrounding tissue.
Image-Guided Therapy and Clinical Translation
A major milestone in this research is the development of 64Cu-labeled porphysomes for positron emission tomography (PET) imaging. By integrating copper-64, a positron-emitting isotope, into the porphyrin core, Dr. Zheng’s team achieved quantitative imaging of nanoparticle biodistribution — without altering the nanoparticle’s pharmacology or safety profile.
In preclinical models (rats, dogs, rabbits), 64Cu-porphysomes exhibited:
- Stable radiolabeling (<0.01% labeling ratio);
- Predictable pharmacokinetics identical to unlabeled porphysomes;
- Accurate tumor visualization across multiple cancer types (prostate, oral, bone metastasis).
These data paved the way for Health Canada’s approval of a Phase 1a/1b human trial, designed with an innovative parallel structure — once safety is confirmed in one cancer type, imaging and treatment trials can immediately begin across others.
According to Dr. Zheng, “64Cu-porphysomes are both diagnostic and therapeutic — they enable imaging-based dosimetry, patient stratification, and personalized treatment all in one.”
Next-Generation Porphysomes: Expanding the Theranostic Landscape
As the field of nanotheranostics evolves, Dr. Gang Zheng’s laboratory continues to push the boundaries of what lipid-based nanostructures can achieve. While the first-generation porphysomes already combine light-triggered therapy and multimodal imaging, next-generation porphysomes are designed to respond intelligently to physiological cues and to integrate new diagnostic and therapeutic functions. These innovations collectively expand the theranostic landscape of lipid nanoparticles.
J-Porphysomes: Photosynthesis-Inspired Thermal Sensors
The J-porphysome is a remarkable example of biomimetic engineering. Inspired by how nature organizes chlorophyll molecules in photosynthesis, the Zheng Lab developed porphysomes capable of forming J-aggregates—ordered molecular stacks that shift optical properties depending on their microenvironment. This unique structure enables J-porphysomes to act as photoacoustic thermal sensors.
When illuminated, they absorb light and convert it into heat for photothermal therapy (PTT). As the temperature rises, the aggregates disassemble, decreasing light absorption and effectively shutting off further heating—a built-in thermal self-regulation mechanism. Once the temperature drops, the aggregates reassemble and the cycle restarts. This behavior ensures safe, efficient photothermal treatment without the need for external temperature control.
Nanotexaphyrins: Broadening Metal Chelation and Radiosensitization
To extend porphysome functionality into radiotherapy, Dr. Zheng’s group introduced nanotexaphyrins, enlarged porphyrin analogs capable of chelating diverse metal ions such as gadolinium (Gd) or lutetium (Lu). These metal-porphyrinoid complexes provide MRI visibility, radiosensitization, and even oxygen-carrying capacity to overcome tumor hypoxia.
In preclinical studies, Gd-nanotexaphyrins enhanced radiation response and prolonged survival in non-small-cell lung cancer (NSCLC) models with brain metastases. Their ability to modulate oxygen levels exemplifies how rational nanostructure design can achieve synergistic multimodal therapy.
BODIPYsomes: Porphyrin-Free Optical Stability
Beyond porphyrin chemistry, the Zheng Lab has pioneered BODIPYsomes—lipid nanoparticles built from aza-BODIPY-lipids, the first porphysomes without porphyrins. Through J-dimerization, these nanoparticles exhibit exceptional optical stability, maintaining bright and stable signals for photoacoustic and fluorescence imaging simultaneously.
Together, these next-generation systems—J-porphysomes, nanotexaphyrins, and BODIPYsomes—represent a modular toolkit for designing multifunctional, stimuli-responsive, and image-guided lipid nanoparticles. They embody the future of personalized nanotheranostics, where therapy and diagnostics are seamlessly integrated within a single, adaptive nanoplatform.
Addressing Translation Challenges in Theranostic Nanomedicine
While the progress in theranostic lipid nanoparticles (LNPs) is extraordinary, translating these complex systems from academic discovery to clinical practice remains a formidable challenge. Dr. Gang Zheng emphasized that scientific innovation must be matched with manufacturing rigor, reproducibility, and regulatory readiness for true clinical success. His experience developing porphysomes into a first-in-human study offers valuable insight into overcoming these barriers.
1. Chemical Precision and Reproducibility
One of the key hurdles in nanomedicine translation lies in ensuring molecular uniformity. Even subtle differences in lipid chemistry — such as positional isomers in porphyrin-lipid conjugates — can dramatically alter the biodistribution, pharmacokinetics, and toxicity of nanoparticles in vivo.
In the early porphysome studies, the presence of mixed regioisomers complicated the understanding of structure–activity relationships. Dr. Zheng’s team addressed this by developing a 200-gram scale synthesis of the pure sn-2 isomer of pyro-lipid, eliminating heterogeneity and improving in vivo predictability. This achievement demonstrated that large-scale, high-purity synthesis is not only possible but essential for clinical-grade nanomedicine production.
2. Regulatory Acceptance and Clinical Strategy
Theranostic agents occupy a unique regulatory niche. They simultaneously behave as drugs, imaging agents, and sometimes devices, creating uncertainty in how agencies evaluate safety and efficacy.
Dr. Zheng’s approach — radiolabeling porphysomes with trace amounts (<0.01%) of 64Cu — elegantly addressed this issue. Since the radiotracer did not alter the nanoparticle’s pharmacology, 64Cu-porphysomes and unlabeled porphysomes were considered pharmacologically equivalent. This design allowed regulators to treat the compound as a true imaging tracer with well-understood toxicology, simplifying approval pathways and enabling a seamless transition to human testing.
The Health Canada–approved Phase 1a/1b clinical study leverages imaging-based pharmacokinetic analysis to identify optimal dosing and tumor uptake in real time. Once safety is confirmed, the modular trial design allows simultaneous testing across multiple cancer sites, accelerating translation without compromising safety.
Conclusion: Translating Innovation into Impact
The story of theranostic lipid nanoparticles—from laboratory discovery to clinical translation—epitomizes the evolution of nanomedicine into a mature, multidisciplinary science. Through his pioneering work, Dr. Gang Zheng has demonstrated that nanostructures can be intelligently engineered not only to deliver drugs but also to visualize disease, monitor therapy, and adapt treatment dynamically.
- From porphysomes with light-triggered imaging and therapy, to radiolabeled 64Cu-porphysomes that enable real-time PET imaging and clinical translation, and to next-generation J-porphysomes, nanotexaphyrins, and BODIPYsomes with smart, stimuli-responsive behaviors—each innovation expands the boundaries of what lipid-based nanoplatforms can achieve.
- More importantly, these advances highlight the power of integration: combining chemistry, imaging, biology, and clinical science to create truly multifunctional therapeutic systems. Such integration paves the way toward a new era of personalized nanotheranostics, where every patient’s treatment is guided by molecular imaging and tailored therapeutic response.
BOC Sciences: Accelerating Lipid-based Nanoparticle Innovation
At BOC Sciences, we share the vision of accelerating the translation of nanomedicine innovations like theranostic lipid nanoparticles from concept to clinical reality. Our comprehensive Lipid Nanoparticle (LNP) & Liposome CDMO services provide end-to-end support for researchers and pharmaceutical developers worldwide.
We specialize in:
- Custom lipid synthesis and formulation optimization
- Payload encapsulation and release profiling for drugs, nucleic acids, and imaging agents
- Process scale-up and GMP manufacturing under strict quality assurance
- Analytical characterization, stability, and regulatory documentation
With extensive expertise across liposome and lipid nanoparticle technologies, BOC Sciences empowers partners to advance their therapeutic and diagnostic platforms efficiently, safely, and compliantly.
To explore more about our services or view Dr. Zheng’s full webinar presentation, visit the webinar page of “Theranostic Lipid Nanoparticles for Cancer Medicine” .
Together, we are shaping the future of smart, image-guided, and personalized nanomedicine—one lipid nanoparticle at a time.