Advances in Chiral Construction and Biochemical Applications of

Chiral Gold Nanoparticles

Jinpeng Huang

1,*

and Haowen Zhang

School of Science, Southern University of Science and Technology, Shenzhen, Guangdong, 518055, China

School of Materials Science and Engineering, Tianjin University of Technology, Tianjin, 300384, China

Keywords: Chiral Gold Nanoparticles, Chiral Origin, Enantiomer Recognition, Asymmetric Catalysis, Tumor Chiral

Phototherapy.

Abstract: Chiral gold nanoparticles (AuNPs) leverage nanoscale geometric asymmetry to amplify chirality-encoded

functions, bridging molecular stereochemistry with plasmonic material properties. Their chirality arises from

helical surface nanostructures or ligand-induced asymmetry, enabling strong chiroptical responses via

plasmon-exciton coupling and circular dichroism enhancement. Bottom-up synthesis strategies—such as

chiral ligand templating (e.g., cysteine, peptides) directing atomic lattice distortion, enantioselective growth

on chiral seeds, and plasmon-guided self-assembly of achiral units into supramolecular helices—allow precise

control over 3D chiral geometries. These architectures interact selectively with biomolecules through

stereocomplementary interfaces, enhancing enantiomer discrimination (e.g., drug detection at ppm levels) and

enabling chirality-dependent cellular uptake. In photomedicine, chiral AuNPs exploit plasmon-enhanced

circularly polarized light absorption for targeted photothermal therapy and ROS generation, while their

asymmetric catalytic sites promote stereoselective synthesis. However, challenges include weak interfacial

chirality transfer, limited dynamic reconfiguration of chiral fields, and signal attenuation in biological

environments. Advancing in situ chiral monitoring (e.g., chiral SERS) and adaptive chirality modulation via

stimuli-responsive ligands could unlock applications like real-time chiral biomarker tracking and logic-gated

nanomedicine. Integrating nanoscale chirality with quantum plasmonics further positions chiral AuNPs as

multifunctional platforms for beyond-molecular stereochemical engineering.

1 INTRODUCTION

Chirality, a geometric property describing non-

superimposable mirror-image configurations,

manifests as left- and right-handed enantiomers. A

striking example is the Chrysina gloriosa beetle,

whose chiral exoskeleton exhibits polarization-

dependent coloration—vivid under left-handed

circularly polarized light but muted under right-

handed polarization—demonstrating chirality-driven

optical anisotropy. While early chirality research

focused on biomacromolecules (proteins/DNA),

advances in nanophotonics have enabled chiral

engineering in inorganic systems. AuNPs overcome

traditional limitations: Unlike biomolecules requiring

millimolar concentrations for detectable circular

dichroism, AuNPs amplify chiroptical signals 10³–

https://orcid.org/0009-0001-3280-1692

https://orcid.org/0009-0004-4031-9347

10⁶-fold via localized surface plasmon resonance

(LSPR) at 500–1200 nm wavelengths. This LSPR-

enhanced chirality originates from asymmetric

electron oscillations that magnify molecular

asymmetry into macroscopic optical effects,

achieving label-free chiral detection at sub-

nanomolar levels, surpassing conventional

spectroscopy by three orders of magnitude. To

harness this plasmonic amplification, researchers

now engineer programmable chiral architectures

through innovative nanofabrication approaches.

By integrating chiral inducers (e.g., thiolated

peptides, helical polymers) with synthetic

strategies—including seed-mediated chiral growth,

ligand-directed assembly, and plasmon-coupled

superlattice engineering—researchers achieve

precise control over AuNP chirality. These systems

476

Huang, J. and Zhang, H.

Advances in Chiral Construction and Biochemical Applications of Chiral Gold Nanoparticles.

DOI: 10.5220/0013827800004708

Paper published under CC license (CC BY-NC-ND 4.0)

In Proceedings of the 2nd International Conference on Innovations in Applied Mathematics, Physics, and Astronomy (IAMPA 2025), pages 476-481

ISBN: 978-989-758-774-0

unlock transformative applications spanning

enantioselective recognition through differential

molecular adsorption, asymmetric photocatalysis

mediated by spin-polarized hot carrier dynamics, and

chirality-programmed tumor therapies that synergize

circularly polarized light penetration with

stereospecific immune modulation, each leveraging

nanoscale chiral topology to manipulate light-matter

interactions at subwavelength scales.

Recent advances in chiral AuNP synthesis have

enabled precise control over geometric

configurations and chiroptical properties through

chiral inducers and innovative strategies like seed-

mediated chiral growth, ligand-directed assembly,

and plasmon-coupled superlattice engineering. These

methods yield helical, twisted, or chiral-groove

nanostructures with enhanced circular dichroism (g-

factors: 0.1–0.3). Leveraging LSPR, chiral AuNPs

amplify optical signals by 10³–10⁵-fold, surpassing

traditional molecular chirality detection limits.

Applications include enantioselective recognition via

differential molecular adsorption, asymmetric

photocatalysis with spin-polarized hot carriers (85%

ee in CO₂ reduction), and chirality-dependent

photothermal therapies, achieving >40% tumor

ablation efficiency in vivo. These breakthroughs

highlight chiral AuNPs as transformative tools in

nanophotonics, catalysis, and biomedicine, bridging

fundamental chirality studies to functional device

engineering.

2 CHIRALITY SOURCES OF

CHIRAL GOLD

NANOPARTICLES

2.1 Ligand-Induced Chirality

Surface plasmon-coupled chiral enhancement has

emerged as a transformative strategy for amplifying

chiral signatures and shifting them into the visible

spectral region. Studies have elucidated that intimate

coupling between metal nanoparticles and chiral

biomolecules enables UV chiral signatures to couple

with LSPR frequencies (Zhang & Govorov, 2013).

This phenomenon arises from "hotspot" regions

between nanoparticles, which amplify local electric

fields through plasmonic coupling. Building on this,

Kneer et al. (2018) positioned DNA between

gold/silver nanoparticles (spherical/rod-shaped) and

used computational modeling to confirm that hotspot-

mediated field enhancement in assemblies can

amplify molecular chiral signals by orders of

magnitude compared to single particles. The study

highlighted how nanoparticle morphology and

spacing modulate plasmonic coupling and chiral

signal strength (Figure 1 a-b).

Zhang et al. (2023) reported chiral signal transfer

from thiol molecules to gold nanorod assemblies by

incorporating chiral thiol molecules into side-by-side

assemblies of achiral gold nanorods. Their study

revealed that while chiral thiol molecules played a

critical role in generating chiral signals in the

assemblies, the achiral CTAB ligands on gold

nanorod surfaces also exerted significant influence.

The formation of dense chiral ligand shells was found

to facilitate efficient chiral transfer from adsorbed

thiol molecules to the nanorod assemblies, enabling

circular dichroism (CD) signal amplification. This

work provided guidelines for chiral signal

enhancement through manipulating achiral surface

ligands.

Ligand-induced chirality represents a classic

approach for transferring molecular chirality to the

nanoscale and remains the most widely used method

for constructing chiral nanoparticles. Such chiral

nanomaterials have found extensive applications in

chiral sensing, detection, and biomedical research.

However, nanoparticles prepared with this method

generally exhibit low anisotropy factors and pose

challenges for characterization by electron

microscopy, limiting mechanistic understanding of

their chiral origination.

2.2 Colloidal Self-Assembly

Plasmonic CD signals in the visible range can be

induced by coupling chiral small molecules with gold

nanoparticles; however, this methodology encounters

significant limitations. Specifically, the strategy

demands both the well-ordered orientation of chiral

ligands on nanoparticle surfaces and spectral overlap

between molecular vibrations and plasmonic modes,

which often results in suboptimal coupling efficiency

and correspondingly weak CD responses. Hopefully,

Chiral ligand-directed self-assembly yields rather

enhanced CD-active chiral nanostructures.

In Fei's (2019) experiment of modifying AuNP

colloidal solutions with NaC, due to the amphiphilic

nature of NaC molecules, the NaC molecules

adsorbed on the surface of gold nanoparticles can

interact with those on the surface of adjacent

nanoparticles through hydrophobic forces leading to

the aggregation of nanoparticles. It is noteworthy that

when the concentration of NaC is relatively high (24

mM), the generated AuNPs tend to be smaller. Sun et

al. (2016) prepared a chiral gold nanohybrid dimer

Advances in Chiral Construction and Biochemical Applications of Chiral Gold Nanoparticles

477

architecture. This dimeric system consists of two gold

nano-ellipsoids: one functionalized with a telomerase

primer and the other conjugated with linker-

complementary DNA strands. These nanostructures

self-assemble into a scissor-shaped configuration

under linker DNA mediation. The resulting dimer

exhibits robust chiral optical responses in the visible

spectrum, enabling intracellular telomerase activity

quantification (Figure 2a-b).

In addition, DNA Origami, proposed by

Rothemund (2006), introduced a novel self-assembly

approach. And Liu and Ding (2012) further

developed adjustable helical structures by curving 2D

DNA origami into nanotubes and positioning gold

nanospheres (Figure 2c). Liu et al. (2016) created

circular 3D assemblies by combining four curved

DNA origami units, resulting in left/right-handed

helices with 24 spirally arranged particles (Figure 2

d). These multi-unit constructs generated stronger CD

responses than monomeric counterparts.

By transforming disordered ligand-NP systems

into structured, highly active chiral plasmonic

platforms, colloidal self-assembly paves the way for

advanced applications in ultrasensitive sensing,

nanophotonics, and beyond, where tunable and robust

optical properties are critical.

Figure 1: (Color online) Chiral induction by ligands. (a) An

origami sheet composed of multiple parallel b-type DNAs;

(b) DNA-functionalized gold nanospheres or nanorods; (c)

TEM images of dimer structures of gold nanospheres or

nanorods; (d) Schematic representation of a "hot spot"

region between two nanoparticles generating a strong

electric field (Kneer et al., 2018).

Figure 2: (Color online) Chiral induction of AuNPs by self-

assembly. (a) Schematic of intracellular quantitative

detection of telomerase using gold heterodimers. (b)

Corresponding data of telomerase activity measured in

various cells with this nanoplatform. (Sun et al., 2016) (c)

DNA origami nanoparticle helices. (Liu and Ding, 2012)

(d) TEM diagram of the ring structure of left and right-

handed nanoparticles. (Liu et al., 2016)

2.3 Intrinsic Chiral Crystal Structure

Despite significant advancements in chiral gold

nanomaterials through coupling and self-assembly

strategies, persistent challenges—including

inadequate chiral induction and structural instability,

particularly in complex DNA-templated protocols—

necessitate alternative approaches. Direct synthesis of

inherently chiral AuNPs with precisely controlled

morphologies has emerged as a critical frontier to

address these limitations.

Innovative work by Wang et al. (2014) revealed

that asymmetric chiral cores can exist in gold clusters,

distinct from symmetric cores stabilized by chiral

ligand shells. Using a tetradentate organophosphorus

ligand (PP3), they synthesized chiral Au20

nanoclusters via direct reduction. Structural analysis

revealed the Au20 core comprises two subclusters: an

icosahedral Au13 (orange spheres) and a Y-shaped

Au7 (green spheres) in Figure 3 (a). The helical

arrangement of the Y-shaped Au7 subcluster imparts

C3 symmetry to the entire Au20 core, providing

definitive structural evidence for inherently chiral

gold clusters. The multidentate phosphine ligands

enhance cluster stability through chelation, opening a

path to design gold clusters with purely inorganic

chiral cores for applications in catalysis and sensing.

Lee et al. (2018) demonstrated another

breakthrough by fabricating chiral propeller-shaped

gold nanoparticles (with g-factors ≈ 0.2) using

glutathione-mediated growth on octahedral seeds

(Figure 3 b-c). The particle's slit-rich architecture

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generates intense electromagnetic coupling between

adjacent nanosheets, amplifying CD responses. This

strategy induces helical morphologies in

nanoparticles, presenting a scalable method for 3D

chiral structures with high optical activity.

Figure 3: (Color online) AuNPs with structural chirality.

(Wang et al., 2014) (a) Au20 model: The purple spheres are

phosphorus atoms, and the gray spheres are carbon atoms.

(b-c) SEM images and geometric models. (Lee et al., 2018).

3 ADVANCES IN THE

APPLICATION OF CHIRAL

AUNPS

3.1 Enantiomer Recognition

Conventional molecular chirality exhibits suboptimal

signal intensity in the visible spectral region,

hindering its practical implementation in chiral

sensing applications. However, the synergistic

combination of chiral molecules with plasmonic

AuNPs generates enhanced chiral signals in the

visible range, which are highly responsive to

geometric variations of nanoparticles and

environmental changes. This property enables

development of ultrasensitive chiral biosensors.

Kang’s group (2010) fabricated an

electrochemical sensor using penicillamine-

functionalized AuNPs (Pen-AuNPs) for

enantioselective recognition of 3,4-

dihydroxyphenylalanine (DONP). Small-sized Pen-

Au NPs with a single enantiomeric ligand only

promote the redox reaction of one enantiomer of

DONP. The study also found that the size of Pen-Au

NPs affects their enantioselectivity performance.

Specifically, smaller Pen-Au NPs show better

selectivity for L- and D-DOPA.

Tang et al. (2025) utilized L-cysteine-

functionalized AuNPs as colorimetric probes for

rapid R/S-phenylalaninol and R/S-ibuprofen

detection, which could develop into purity detection

so as to ensure drug therapeutic effects while limiting

side effects. And it is assumed that when chiral

AuNPs recognize enantiomers, non-covalent

interactions induce energy resonance transfer on the

surface of nanomaterials, leading to their aggregation

and color changes. Li et al. (2022) synthesized helical

gold nanoparticles with intrinsic chirality and

constructed a chiral sensor for discriminating L-

tyrosine from D-tyrosine. Notably, differential pulse

voltammetry revealed nearly sixfold differences in

peak currents between tyrosine enantiomers, enabling

accurate determination of enantiomeric purity and

composition. The chiral electrode developed also

enabled quantification of L-tyrosine in

pharmaceutical capsules, opening new avenues for

chiral enantiomer recognition in biomedical and

pharmaceutical fields.

3.2 Asymmetric Catalysis

Chiral metallic nanomaterials exhibit unique size-

dependent optical and catalytic properties distinct

from molecular-scale chirality, offering

transformative opportunities in asymmetric organic

synthesis.

Cui (2015) advanced chiral nanocatalysis by

incorporating a cytosine-derived amphiphilic ligand

(C₈H₄Cyt) into AuNP systems. These chiral AuNPs

displayed superior catalytic activity for p-nitrophenol

reduction by sodium borohydride at ≥ 30 °C,

outperforming conventional AuNPs in both stability

and recyclability. The chiral architecture mitigated

aggregation, maintaining activity even after long-

term storage. Notably, larger chiral nanomaterials

experienced less activity due to decreased accessible

reaction sites, highlighting needs of finer AuNPs

producing method in plasmonic catalysis.

Tan and colleagues (2022) made use of chiral

Au@CdS core-shell nanostructures for asymmetric

photocatalytic water splitting while from Negrín-

Montecelo group (2022), chiral Au and TiO_2

combination irradiated with polarization-matched

circularly polarized light (CPL) exhibit

approximately 2.9-fold higher catalytic efficiency

compared to mismatched polarization conditions,

demonstrating strong selectivity for enantiomeric

interactions. (Figure 4a-b).

Figure 4: (a) Chirality-dependent hydrogen production

efficiency in water splitting. (Tan et al., 2022) (b) Au and

TiO2 for chiral photocatalytic applications. (Negrín-

Montecelo et al., 2022)

Advances in Chiral Construction and Biochemical Applications of Chiral Gold Nanoparticles

479

3.3 Tumor Photothermal Therapy

Accumulating evidence highlights the profound

impact of chirality on nanomaterial performance in

biological systems. In tumor phototherapy using

chiral noble-metal nanostructures, Gao et al. (2017)

engineered DNA-templated self-assembled gold

core-shell satellite nanostructures (Figure 5). Under

circularly polarized light irradiation, these constructs

exhibited enhanced reactive oxygen species (ROS)

generation (roughly two-fold higher than linear

polarization), underscoring chirality's role in

optimizing photodynamic therapy. Additionally,

chiral architecture modulates nanomaterial

biocompatibility and downstream signaling pathways,

overcoming challenges in cancer treatment. Xu et al.

(2022) synthesized AuNPs with record-high g-factors

(0.4), demonstrating chiral-dependent immune

activation: left-handed NPs induced stronger

dendritic cell maturation and pro-inflammatory

cytokine expression compared to right-handed

counterparts. This disparity arises from differential

binding affinity to G-protein-coupled receptors and

accelerated endocytosis rates for left-handed NPs.

In the realm of chiral materials, a larger g-factor

implies less energy dissipation of light energy,

signifying a greater capacity for controlling light

polarization. As depicted in Figure 6, the chiral Au

Helicoids nanoparticles prepared by Weng (2023)

possess a wide-ranging optical absorption spanning

from 550 to 1100 nm and a relatively elevated g-

factor. When excited by 808-nm near-infrared CPL,

the photothermal efficiency of the chiral Au helicoid

nanoparticles demonstrates a distinct chiral disparity.

And the disparity primarily stems from HeLa cells'

higher endocytosis efficiency for L-Au Helicoids

nanoparticles compared to D-Au Helicoids

nanoparticles. In contrast to traditional photothermal

therapy, which frequently inflicts damage on healthy

cells due to the employment of high-power lasers or

prolonged radiation, chiral photothermal therapy can

manifest efficient light-conversion properties and

selective light-absorption characteristics within the

near-infrared region. This can substantially minimize

the damage to normal cells (with a cell survival rate

of around 90.00%) and enhance the inactivation

efficiency of cancer cells (94.95%), which means it

can be harnessed as a secure photothermal conversion

agent for the research on the photothermal

inactivation of tumor cells.

Figure 5: (Color online) Schematic diagram of self-

assembled shell satellite nanostructures as chiral

photodynamic therapeutic agents. (Gao et al., 2017)

Figure 6: (Color online) Schematic diagram of surface

modification of L-/D-Au Helicoids nanoparticles and their

photothermal effects under CPL excitation at 808nm.

(Weng, 2023)

4 CONCLUSION

This review systematically evaluates the synthetic

strategies and emerging applications of AuNPs.

Chiral architectures in AuNPs can arise from

template-directed growth (e.g., helical seed-mediated

synthesis), molecular imprinting with chiral ligands,

or supramolecular self-assembly. These design

principles enable advanced applications in

stereoselective sensing, asymmetric catalysis, and

synergistic photothermal cancer therapy.

Notwithstanding significant progress in chiral

AuNP synthesis and bioanalytical applications,

critical challenges persist. Current methods for

producing AuNPs with uniform chiral configurations

and robust chiroptical activity remain inefficient and

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scalable, while most plasmonic responses occur in the

visible spectrum, limiting deep-tissue penetration in

biomedicine. Additionally, comprehensive

biocompatibility assessments—encompassing long-

term stability, toxicity profiles, and clearance

mechanisms—are underdeveloped. In vitro models

often fail to recapitulate in vivo complexities,

necessitating sophisticated in vivo studies to

characterize size/shape-dependent biodistribution

and enantioselective biological effects.

To address these challenges, future research

should focus on developing Chiral AuNPs with

enhanced near-infrared (NIR) chiroptical activity,

advancing surface functionalization for non-toxicity

and targeted specificity, elucidating cellular uptake

mechanisms, and fostering interdisciplinary

collaboration to bridge fundamental synthesis with

translational precision medicine applications. Despite

these hurdles, the dynamic field of Chiral AuNP

research continues to hold immense potential for

breakthroughs in biochemical research and clinical

practice.

ACKNOWLEDGEMENTS

All the authors contributed equally and their names

were listed in alphabetical order.

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